Severe, primary dysmenorrhea treated with naproxen. A prospective, double-blind, crossover investigation

26 women aged 15–45 with severe, primary dysmenorrhea were treated with naproxen (NAPROSYN^R, SYNTEX) and placebo during 2 × 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 men-struations 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 dev loped 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.     

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.     

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.     

The relief 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 %) and in 60 of the indomethacin-treated cases (90 %). 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.     

Effect of hydroxypropyl methylcellulose and hydrogenated castor oil on naproxen release from sustained-release tablets

The effect of the concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic (hydrogenated castor oil [HCO]) products, fillers (lactose and dibasic calcium phosphate), and buffers (sodium bicarbonate, calcium carbonate, and sodium citrate) on naproxen release rate was studied. Matrix tablets were prepared by double compression, andIn vitro dissolution tests were performed. The dissolution results showed that an increased amount of HPMC or hydrogenated castor oil resulted in reduced drug release. The inclusion of buffers in the HPMC matrix tablets enhanced naproxen release. For HCO tablets, only sodium bicarbonate enhanced naproxen release. The presence of lactose on HPMC matrix tablets did not show a significantly different result from that obtained with the formulation containing dibasic calcium phosphate as a filler. However, for the tablets containing HCO, the presence of lactose significantly enhanced the naproxen release rate. The matrix-forming materials in this study were suitable for use in sustained-release tablets containing naproxen. The drug release can be modulated by adding suitable amounts of diluents and buffers.     

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.     

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).     

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.     

Comparison between daidzein and genistein antioxidant activity in primary and cancer lymphocytes

The main objective of this study was to compare the protective effect of daidzein and genistein against induced oxidative damage in Jurkat T-cell line and in peripheral blood lymphocytes of healthy subjects. After supplementation of cells with isoflavones (from 2.5 to 20micromol/L in Jurkat T-cell and from 0.01 to 2.5micromol/L in primary lymphocytes, 24h), we determined DNA damage induced by hydrogen peroxide using the comet assay and lipid peroxidation evaluating malondialdehyde (MDA) production after ferrous ion treatment. Supplementation of Jurkat cells and primary lymphocytes with both isoflavones significantly increased DNA protection from oxidative damage at concentrations between 0.1 and 5micromol/L (P<0.05), and with just daidzein, at concentrations higher than 2.5micromol/L, there was a decrease in the production of MDA (P<0.05). Our results seem to support that daidzein is just as effective as genistein in protecting cells against oxidative damage especially with respect to DNA. Moreover, since the protective effect was found at concentrations reachable in plasma after soy consumption (less than 2micromol/L), it can be assumed that the antioxidant activity of isoflavones could really contribute to the healthy properties of soy.     

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。     

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.     

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.     

Paeonol alleviates primary dysmenorrhea in mice via activating CB2R in the uterus

Background and purposePrimary dysmenorrhea is the most common gynaecologic problem in menstruating women and is characterized by spasmodic uterine contraction and pain symptoms associated with inflammatory disturbances. Paeonol is an active phytochemical component that has shown anti-inflammatory and analgesic effects in several animal models. The aim of this study was to explore whether paeonol is effective against dysmenorrhea and to investigate the potential mechanism of cannabinoid receptor signalling.Experimental approachDysmenorrhea was established by injecting oestradiol benzoate into female mice. The effects of paeonol on writhing time and latency, uterine pathology and inflammatory mediators were explored. Isolated uterine smooth muscle was used to evaluate the direct effect of paeonol on uterine contraction.Key resultsThe oral administration of paeonol reduced dysmenorrhea pain and PGE2 and TNF-α expression in the uterine tissues of mice, and paeonol was found to be distributed in lesions of the uterus. Paeonol almost completely inhibited oxytocin-, high potassium- and Ca²⁺-induced contractions in isolated uteri. Antagonists of CB2R (AM630) and the MAPK pathway (U0126), but not of CB1R (AM251), reversed the inhibitory effect of paeonol on uterine contraction. Paeonol significantly blocked L-type Ca²⁺ channels and calcium influx in uterine smooth muscle cells via CB2R. Molecular docking results showed that paeonol fits well with the binding site of CB2R.Conclusions and implicationsPaeonol partially acts through CB2R to restrain calcium influx and uterine contraction to alleviate dysmenorrhea in mice. These results suggest that paeonol has therapeutic potential for the treatment of dysmenorrhea.     

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 of natural and synthetic prostaglandin E2 tablets in labour induction.

A multicentre, randomized, double-blind trial compared the efficacy and safety of and tolerance to natural and synthetically produced prostaglandin E2 tablets in the induction of labour in 202 women. The compounds were similarly effective, inducing labour in approximately 66% of patients. The total dose required and the interval between induction and delivery were similar in the two groups, as were the Apgar scores at 1 and 5 minutes and the incidence of maternal and fetal side effects.