The refief of primary dysmenorrhea by ketoprofen and indomethacin

The prostaglandin biosynthesis inhibitors ketoprofen and indomethacin were compared in the treatment of primary dysmenorrhea in a double-blind, cross-over trial involving 23 patients. Each drug was used for 2-4 days during 3 consecutive menstruations in randomized order. Good or moderate overall relief was obtained in 60 of the 68 ketoprofen-treated menstruations (88%). A dysmenorrhea score, based on subjective estimations of 8 symptoms, similarly decreased from a mean (+/- S.E.M.) basal level of 9.6 +/- 0.6 to 3.6 +/- 0.3 during ketoprofen treatment and to 4.0 +/- 0.3 during indomethacin. Both drugs relieved pelvic and lower back pains and eliminated vomiting and diarrhea in 82-97% of the cycles whereas headache, fatigue and nervousness were less frequently alleviated (40-67%). Eighteen of the 23 women (78%) had been unable to work during the first day of menstruation, the rate of working days lost was reduced to 4% with ketoprofen and 9 with indomethacin. Mild side-effects occurred during 12 ketoprofen and 14 indomethacin therapies. Ketoprofen thus seems to be as effective and tolerable as indomethacin in the treatment of primary dysmenorrhea.     

Efficacy of ketoprofen in treating primary dysmenorrhea.

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.     

Prostaglandins,indomethacin and dysmenorrhea

Uterine contractility was recorded during the period of menstruation in six dysmenorrheic women. A variable high tonus was observed in each case. Uterine recordings were repeated during the subsequent menstruation following pre-treatment with indomethacin at an oral dose of 75 mg or 200 mg per day beginning one day before the expected onset of menstruation. A lower uterine tonus was found in all indomethacin-treated cycles. Complete alleviation of spasmodic pain was obtained in the six subjects. The endogenous concentration of 15-keto-13,14-dihydro PGF_2α was determined by the gas chromatography-mass spectrometry method and observed to be relatively high in women with dysmenorrhea.     

Comparison between naproxen tablets and suppositories in primary dysmenorrhea

Naproxen tablets and suppositories were compared, in the treatment of primary dysmenorrhea, in a double-blind cross-over trial. The results on 32 patients treated during 128 menstruations with either tablets and suppositories were analysed. Both naproxen tablets and suppositories produced a significant but similar overall relief of dysmenorrhea, although the tablets had a better effect in relieving spasmodic pain than the suppositories (p < 0.05). Occasions of failure to obtain relief were not related to the occurrence of vomiting or diarrhea during the trial. Vomiting seems not to be responsible for the therapeutic failures of oral treatments with prostaglandin-synthetase inhibitors in primary dysmenorrhea.     

Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy

A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationship between prostaglandin F and dysmenorrhea is suggested by these studies     

A comparison of skin temperature and EMG training for primary dysmenorrhea

Eleven female volunteers completed a 6-month treatment program consisting of a 2-month baseline phase, 2 months of biofeedback training ( number of sessions=12.9), and 2 months of follow-up data collection. Subjects were assigned to one of two treatment groups: skin temperature training or EMG training of the frontalis muscle. Self-report data were gathered by means of the Symptom Severity Scale. Results, which were analyzed according to a 2×3 (treatment×phase) split-plot factorial design, indicate a highly significant overall treatment effect (F=19.32,p<.001). There was no significant difference between treatments (F=.47) and no significant interaction effect (F=1.74).     

Prostaglandin levels in endometrial jet wash specimens in patients with dysmenorrhea before and after indomethacin therapy.

A patient with functional primary dysmenorrhea of over two years duration was subjected to the endometrial jet wash technique during the period of active menstrual flow. Prostaglandin F analysis of the jet washings revealed significantly elevated levels during menstruation over normal control levels. Following indomethacin therapy, jet wash prostaglandin F levels were dramatically reduced and the patient became asymptomatic. A cause and effect relationsship between prostaglandin F and dysmenorrhea is suggested by these studied.     

Comparison between fluproquazone and indomethacin in treatment of primary dysmenorrhoea

Two prostaglandin synthesis inhibitors, fluproquazone (100 mg) and indomethacin (25 mg), were compared in a double-blind, crossover study for treatment of primary dysmenorrhoea in 31 patients. Each drug was used during two consecutive menstruations in randomized order. Both treatments significantly relieved spasmodic pains and other dysmenorrhoeic symptoms. No significant differences were found between the treatments in regard to the overall efficacy assessed at the end of each treated cycle. However, 20 patients preferred indomethacin and 7 patients fluproquazone. Three patients reported mild side-effects with fluproquazone as compared to five patients with indomethacin. It is concluded that both treatments can be used for treatment of primary dysmenorrhoea.     

Biofeedback-assisted relaxation training for primary dysmenorrhea: A case study

Primary dysmenorrhea is a familiar complaint to medical practitioners. Recently, behavior therapy has been shown to be an effective treatment for the symptoms of dysmenorrhea. The present case study offers biofeedback-assisted relaxation treatment as an effective alternative treatment. The Menstrual Symptom Questionnaire was used to classify dysmenorrhea as spasmodic or congestive. This classification provides homogeneous groups of patients. The patient in this study had an 18-year history of primary dysmenorrhea that was resistant to hormonal and analgesic treatment. After two months of baseline observation, she was given eight sessions of skin-temperature biofeedback and autogenic training. She reported significant reduction of pain and discomfort with the use of biofeedback-assisted relaxation. Desensitization using visual imagery, an important component of previous therapies, was not used. Further examination of the efficacy of biofeedback-assisted relaxation training for the treatment of both congestive and spasmodic dysmenorrhea is suggested.     

补佳乐联合缩宫素建立小鼠原发性痛经模型

目的建立小鼠原发性痛经模型。方法不同剂量补佳乐给近交系BALB/c小鼠连续灌胃,末次给药后腹腔注射缩宫素,诱发扭体反应,记录扭体潜伏期和扭体次数,筛选最佳条件。结果补佳乐最佳剂量为0.5 mg/kg;催产素最佳剂量为每只2 U;补佳乐灌胃后1 h为观察扭体反应的最佳时间,用药周期第3天时扭体次数开始增多;从第4天开始维持在高水平。结论补佳乐联合缩宫素可以成功建立小鼠原发性痛经模型。     

Increased rate of primary dysmenorrhea in women with spontaneous premature labor

Prostaglandins (PG) are responsible for primary dysmenorrhea and may be involved in the start of preterm or fullterm labor. Therefore, in order to see if there is any association between these two PG-mediated conditions, the incidence of dysmenorrhea in 177 primiparous women with threatened premature labor was compared with that in 177 primiparous women without premature uterine contractions. Dysmenorrhea had occurred about two times more commonly in women with threatened or established premature labor than in the controls.If this finding is confirmed in prospective studies, dysmenorrhea should be regarded as a factor predisposing women to premature labors.     

Biofeedback-assisted relaxation training for primary dysmenorrhea: a case study.

Primary dysmenorrhea is a familiar complaint to medical practitioners. Recently, behavior therapy has been shown to be an effective treatment for the symptoms of dysmenorrhea. The present case study offers biofeedback-assisted relaxation treatment as an effective alternative treatment. The Menstrual Symptom Questionnaire was used to classify dysmenorrhea as spasmodic or congestive. This classification provides homogeneous groups of patients. The patient in this study had an 18-year history of primary dysmenorrhea that was resistant to hormonal and analgesic treatment. After two months of baseline observation, she was given eight sessions of skin-temperature biofeedback and autogenic training. She reported significant reduction of pain and discomfort with the use of biofeedback-assisted relaxation. Desensitization using visual imagery, an important component of previous therapies, was not used. Further examination of the efficacy of biofeedback-assisted relaxation training for the treatment of both congestive and spasmodic dysmenorrhea is suggested.     

The prevention of benzene-induced genotoxicity in mice by indomethacin

Benzene is a myelotoxin which affects hemopoietic progenitor cells leading to bone-marrow depression as well as a genotoxin which causes chromosomal abnormalities including micronucleus formation. We have demonstrated previously that benzene administered to DBA/2 or C57B1/6 mice causes bone-marrow depression and increased prostaglandin E2 levels in bone marrow; both of these effects can be prevented by the coadministration of indomethacin, a selective inhibitor of prostaglandin synthase. We report, herein, that benzene (400-600 mg/kg body weight), under conditions where it depresses bone-marrow cellularity, also induces an increase in the frequency of micronucleus formation in polychromatic erythrocytes of C57B1/6 mice which is also prevented by the coadministration of indomethacin at levels that do not inhibit cytochrome P450 or myeloperoxidase. In Swiss Webster wild-type mice doses of benzene from 400 to 1000 mg/kg were without effect on marrow cellularity, but did induce the formation of micronucleated polychromatic erythrocytes which could be prevented by indomethacin. In contrast, DBA/2 mice, a strain highly sensitive to benzene, exhibited significant bone-marrow depression at a dose of benzene of 100 mg/kg body weight. Even at this low dose, benzene is too toxic toward developing erythrocytes to allow the evaluation of micronucleus formation. The frequency of induction of micronucleated polychromatic erythrocytes by benzene thus depends on the strain of mouse used. Furthermore, micronucleus formation appears to be an early and very sensitive indicator of benzene toxicity. A possible role for prostaglandin H synthase in the geno- and myelo-toxicity of benzene is discussed.     

Specific physiological responses in women with severe primary dysmenorrhea during the menstrual cycle

This study examined the specific physiological responses of women with primary dysmenorrhea during the severely painful menstrual (days 1-2 of menstruation) and the non-painful follicular phases (days 5-8 after the onset of menstruation). Subjects consisted of 10 severe primary dysmenorrheic (Group P) and 10 non-dysmenorrheic women (Group C) with regular menstrual cycles. However, only 9 out of 10 and 8 out of 10 subjects of Groups P and C participated during the follicular phase. Physiological measures were taken in a resting state for 60 min. In the menstrual phase, the pain ratings and secretory immunoglobulin A (s-IgA) concentrations of Group P were significantly higher than those of Group C, with relatively significant decreases in the leg-skin temperature in the former as well. In addition, the systolic (SBP) and diastolic blood pressure (DBP) at 45 min after rest in Group P were significantly higher than those found in Group C. These reactions strongly suggest activation of the sympathetic-adrenal-medullary axis (SAM axis) by painful stress. Furthermore, the low-frequency (LF) component of the SBP variability (SBPV) was significantly higher in Group P than Group C, even during the follicular phase. These findings imply that Group P may well have elevated activities of the SAM axis throughout the whole menstrual cycle. As such, it suggests that dysmenorrheic women may be affected by certain stressors other than pain per se and pain-derived emotions throughout the whole menstrual cycle. The findings also indicate that women with dysmenorrhea have more sensitive responses to the SAM system than non-dysmenorrheic women during stress. Moreover, the high-frequency (HF) component of heart rate variability (HRV), or the index for the vagus nerve activity, displayed a consistently higher value in Group P than C. It is postulated that the human body may have responded to pain in an attempt to maintain the homeostatic state by enhancing vagus nerve activity.     

Induction of antitumor immunity by indomethacin

Irradiated tumor cells given, together with indomethacin, to syngeneic mice induced an antitumor response and conferred protection against a challenge of a lethal dose of murine mammary (4T1) and lung (3LL) carcinoma cells. Continuous administration of indomethacin was crucial throughout the entire period of immunization and challenge, as no protection was achieved when the drug was given during only one of these procedures. Antitumor immunity was long-lasting and, when tested in the 4T1 model, 48% of mice were resistant to a second challenge of lethal tumor cells. Tumor-free immune mice that were given indomethacin for more than 300 days remained healthy with normal white blood cell counts and normal spleen size. Cells isolated from immune mice were able to kill tumor cells in culture after in vitro activation by interleukin-2, in a manner similar to cells from naive normal control mice. In addition, the mitogenic response of their T cells was as high as that of the control naive mice. While indomethacin was able to induce antitumor immunity to 4T1 and 3LL murine carcinoma cells, both of which contain a high concentration of endogenic prostaglandin E₂ (PGE2), no such immunity was achieved to murine tumor cells with a low concentration of endogenic PGE2. These results suggest a correlation between PGE2 concentration and the ability of indomethacin to induce antitumor immunity. We therefore suggest that an immunotherapy protocol with long-term dispensation of a tolerable dose of an immunomodulator, given together with irradiated autologous tumor cells, may stimulate antitumor responses to tumors containing high concentrations of endogenic PGE2. Received: 12 August 1999 / Accepted: 21 September 1999     

The effect of indomethacin on colony-stimulating-factor production by the lung.

In this study, indomethacin was used to investigate the production of colony-stimulating-factor by the lung tissue. Addition of various concentrations of indomethacin (10(-5)-1 mg/ml) to the lung culture showed that it enhances CSF production in a dose dependent manner. The number of colonies reached a maximum at 1 microgram/ml and gradually diminished at higher concentrations. Addition of exogenous E-series prostaglandins alone had no effect on the CSF activity of normal lung. However, in the presence of indomethacin, E-series prostaglandins reversed the enhancing effect produced by indomethacin. On the other hand, cAMP or its dibutyryl derivative also increased CSF production. Removal of alveolar macrophages from the lung by lavaging had no effect on the CSF production by the lung but reduced the enhancing effect of indomethacin by 50%. The results suggest that indomethacin stimulates CSF production and that this process is partially regulated by prostaglandins and cAMP.     

Polarity induced by chloramphenicol and relief by suA

The suA allele, known to relieve polarity in Escherichia coli, also relieves a unique polar effect on E. coli tryptophan operon messenger RNA produced by chloramphenicol.     

Biofeedback treatment of dysmenorrhea

Nine dysmenorrheic women were run in EMG and thermal biofeedback procedures with concurrent autogenic relaxation practice. Significant reductions in subjective estimates of symptomology associated with dysmenorrhea were noted in all subjects. EMG levels correlated positively with the reductions in symptoms. Thermal levels did not correlate with EMG. In fact no consistent patterns in thermal measures were noted. However, thermal biofeedback cannot be ruled out as an effective treatment for dysmenorrhea since reductions in symptoms occurred during thermal biofeedback training. Another significant aspect of the present study is the effectiveness of long treatment procedures. A six month period was employed and significant reductions in symptoms were noted following two months of biofeedback treatment. Finally, the importance of beginning biofeedback treatment prior to onset of menstrual symptoms is indicated.