Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Electroacupuncture with different waveforms for primary dysmenorrhea:A randomized controlled trial

Objective To observe and compare the clinical effects of different electroacupuncture waveforms on primary dysmenorrhea.Methods This was a prospective,randomized,three-group,parallel-controlled trial.Participants with primary dysmenorrhea were randomly divided into dense-sparse wave,continuous wave,and discontinuous wave groups in a 1:1:1 ratio.Two lateral Ciliao(BL 32)points were used.All three groups started treatment 3–5 days before menstruation,once a day for six sessions per course of treatment,one course of treatment per menstrual cycle,and three menstrual cycles.The primary outcome measure was the proportion with an average visual analog scale(VAS)score reduction of≥50%from baseline for dysmenorrhea in the third menstrual cycle during treatment.The secondary outcome measures included changes in dysmenorrhea VAS scores,Cox Menstrual Symptom Scale scores and the proportion of patients taking analgesic drugs.Results The proportion of cases where the average VAS score for dysmenorrhea decreased by≥50%from baseline in the third menstrual cycle was not statistically significant(P>.05).Precisely 30 min after acupuncture and regarding immediate analgesia on the most severe day of dysmenorrhea,there was a statistically significant difference in the dense-sparse wave group compared with the other two groups during the third menstrual cycle(P<.05).Additionally,there was a statistically significant difference between the dense-sparse wave and discontinuous wave groups 24 h after acupuncture(P<.05).Conclusions Waveform electroacupuncture can alleviate primary dysmenorrhea and its related symptoms in patients.The three groups showed similar results in terms of short-and long-term analgesic efficacy and a reduction in the number of patients taking analgesic drugs.Regarding achieving immediate analgesia,the dense-sparse wave group was slightly better than the other two groups.

Wenjing Zhitong recipe exhibits potential anti-primary dysmenorrhea properties by inhibiting COX2 and PKC signaling pathway in rats induced by estradiol benzoate and oxytocin

Objective:To explore the effect and mechanism of action of the Wenjing Zhitong recipe(WZR)in primary dysmenorrhea(PD)treatment.Methods:Uterine contractions were induced by estradiol benzoate and oxytocin in a PD model and WZR was administrated.The rate of change in uterine contractility and the writhing test were used to evaluate the effects of WZR.The serum levels of prostaglandin F_(2a)(PGF_(2a))and prostaglandin E_2(PGE_2),and the activity of cyclooxygenase-2(COX2)were detected by enzyme-linked immunosorbent assay(ELISA).The changes in phosphor-phospholipase C(pPLC/PLC),phosphor-protein kinase C(pPKC/PKC),and connexin 43(CX43)expression were detected using immunohistochemistry and western blot.Results:WZR significantly reduced the rate of change in uterine contractility and writhing times in the PD model.WZR treatment inhibited the enzymatic activity of COX2 and reduced the levels of PGF_(2a),PGF_(2a)/PGE2and COX2 in the PD model.WZR also significantly reduced the expression of pPLC/PLC,pPKC/PKC and CX43.Targeting the inhibition of COX2 activity,caffeic acid and 1-acetyl-β-carboline were validated as the active ingredients in WZR responsible for reducing uterine contractions.Conclusion:WZR attenuated PD by inhibiting COX2 activity,downregulating PGF_(2a)/PGE_2 expression,and inhibiting the PKC signaling pathway.

A comparison of the effect of Vitamin D and Vitamin E supplementations,alone,and in combination,on reducing the intensity and duration of dysmenorrhea in women:A randomized controlled trial

Objective:The aim of this study is to compare the effect of Vitamin D and Vitamin E supplementations,alone,and in combination,on reducing the intensity and duration of dysmenorrhea in women who were referred to the Kowsar gynecological clinics of Shahid Motahari Hospital of Urmia University of Medical Sciences.Materials and Methods:A double-blinded clinical trial was conducted on 112 women with dysmenorrhea who were randomly allocated into the four study groups.Finally,100 women complete the study and received capsules containing a placebo(n=25),1000 IU of Vitamin D(n=25),400 mg of Vitamin E(n=25),and 1000 IU of Vitamin D+400 mg of Vitamin E(n=25)every 24 h for 2 consecutive months at the beginning of the menstrual period.The pain intensity and duration among groups were compared before and after the intervention.Results:The mean menstrual pain duration in all three experimental groups(Vitamin E,Vitamin D,and the combination of them)was lower than the placebo group(all P<0.05),and the mean pain intensity scores in all three experimental groups were significantly lower than the placebo group(all P<0.05).The results(means)for all of the drugs administered at the end of the 2nd month were better than the 1st month(all P<0.01).Conclusions:Vitamin E and Vitamin D,as well as their combination,are recommended as an effective and safe treatment for the management of the complications of dysmenorrhea.

EFFECTS OF ACUPUNCTURE ON THE HYPOTHALAMUS-PITUITARY-OVARY AXIS IN RATS WITH DYSMENORRHEA

Objective To observe the influence of acupuncture on hypothalamus-pituitary-ovary axis （HPOA） in rats with primary dysmenorrhea, and to explore its mechanisms. Methods Effects of acupuncture on the concentration level of β-endorphin （β-EP）, hypothalamic hormone （gonadotropin-releasing hormone, GnRH）, pituitary hormone （GnRH receptor GnRH-R, follicle stimulating hormone FSH, luteinizing hormone LH） and ovarian hormone （estrodiol E2, estrodiol receptor ER, progesterone P and progesterone receptor PR） were observed in dysmenorrheic rats. Results After receiving acupuncture treatment, the levels of 13- EP, GnRH, GnRH-R, FSH, LH, E2, ER, P and PR were changed, and this suggested that acupuncture had a regulative action on HPOA in dysmenorrheic rats. Conclusion The mechanism of acupuncture acting on the HPOA with primary dysmenorrhea might be its regulating role to the gonadal hormone of HPOA and its corresponding receptor expression.

Natural products:a rising star for treating primary dysmenorrhea?

In the current scenario,dysmenorrhea is a very frequent gynecological condition among women.At least one in every four women suffers from severe abdominal cramps,which are referred to as dysmenorrhea or menstrual cramps.Hence,in this review we compile the data from several reviews and research papers about dysmenorrhea,its pathogenesis,along with all treatment approaches.It was found in a survey that normally women treated these cramps with non-steroidal anti-inflammatory medicines or oral contraceptives,but lately it was found that these medications have a 20%to 25%failure rate as well as unpleasant side effects.Hereby,in this review,we concluded all the possible treatments,including pharmacological treatment,non-pharmacological treatment,and herbal treatments for dysmenorrhea.Many women are looking for alternatives to conventional treatments,such as the use of herbs,vitamins,minerals,nutritional supplements,analgesics,anti-inflammatory agents,and aromatherapy agents,which can have a significant impact when taken on a regular basis.The active constituents of these medicinal plants help the body fight cramps and pain associated with menstruation,as well as alleviate these issues in the most calming and effective way possible.

SPECIFIC INHIBITION OF CONNEXIN 43 GENE EXPRESSION AFTER ACUPOINTS AND ACUPUNCTURE TREATMENT FOR PRIMARY DYSMENORRHEA

Objective To investigate the effect of acupuncture treatment on silencing the expression of Oonnexin 43 （Cx43）, and to study the analgesic mechanism of acupuncture treatment for primary dysmenorrhea （PD） in rats. Methods We used estrostilben to develop the model of primary dysmenorrhea in rat, and RNA interference technology to silence the expression of Cx43 in acupoints. Fifty female rats were randomly divided into five groups （n = 10 in each group） ： normal, model, acupuncture, acupuncture ＋ interference and acupuncture＋ interference control group, pSilencer-Cx43-shRNA and pSilencer-Oon-shRNA were injected locally into the acupoints in interference group and interference-control group, respectively. The incidence rate of writhe reaction over the period of 30 min was evaluated. The expression of the oxytocin receptor （OTR） and vasopressin receptor（VasR） in rat myometrium with Semiquantitative RT-POR and immunohistochemistry. Results （1）The mRNA and protein level of Cx43 in acupoints in interference group were significantly lower those of in the acupuncture group （P〈0.05）. There was no significant difference between acupuncture and interference-control group. （2） Acupuncture could significantly prolong the latency period of writhing body and decrease the number of writhing body as compared with that of model group and interference group. （3）The level of OTR and VasR mRNA and protein in the model group were significantly higher （P〈0.05） as compared to normal group. The results in acupuncture group and interference-control group were similar to the normal group. The results in interference group were similar to the model group. Conclusions Acupuncture may be useful in the treatment of the model of primary dysmenorrhea in the rats. Local injection of Cx43 shRNA expression vetor could silence the expression of Cx43 in acupoint and markedly influence acupuncture effect, demonstrating Cx43 is involved in acupuncture effect.

OBSERVATION OF THERAPEUTIC EFFECTS OF Zhìyīn(至阴BL 67) ON 110 CASES OF PRIMARY DYSMENORRHEA WITH ACU-MOXIBUSTION

Objective To observe the clinical efficacy of primary dysmenorrhea treated with acu-moxibus- tion. Methods 220 cases of primary dysmenorrhea were randomized into control group and treatment group, 110 cases in each one. In control group, fenbid was administered. In treatment group, ZhiyTn （至阴 BL 67） was selected in combination of auricular-point pressing therapy. Results The total effective rate was 94.5% in treatment group and was 76. 4 % in control group, indicating very significant difference （P〈0. 01） in com- parison. Conclusion Acu-moxibustion on BL 67 in combination of auricular-point pressing therapy presents definite therapeutic effect on primary dysmenorrhea, thus, this therapy is worth to be promoted entirely in practice.

Effect of Alpinia officinarum Hance alcohol extracts on primary dysmenorrheal

Objective:To study the effect of Alpinia officinarum Hance(A.officinarum) 80% alcohol extract on the primary dysmenorrhea.Methods:A.officinarum 80% alcohol extract were enriched by macroporous adsorption resins.Female mice of primary dysmenorrhea model were established by oxytocin induction; the effects of A.officinarum 80% alcohol extract on primary dysmenorrhea were observed by body twist method; and the homogenate level of prostaglandin F_(2α)(PGF_(2α)),prostaglandin E_2(PGE_2) and Ca^(2+) in the uterus were observed in oxytocin-induced female mice.Results:The writhing frequency of primary dysmenorrhea mice was significantly decreased after treatment of A.officinarum 80% alcohol extract and the level of PGF_(2α),PGE_2 and Ca^(2+) in mice uterus was significantly decreased(P<0.05,P<0.01) in groups of mice treated with middle and high dosage of A.officinarum 80% alcohol extract compared with that of model group.Conclusions:These findings suggest that A.Officinarum 80% alcohol extract can significantly relieve primary dysmenorrhea.

Mediating effect of interpersonal relations on negative emotions and dysmenorrhea in female adolescents

Background Good interpersonal relationships can improve the negative mood and, to a certain extent, may help relieve dysmenorrhea symptoms. However, there has been no study examining the role of interpersonal relationships in dysmenorrhea and how they may interact with negative emotions. Aims To investigate the connection between negative affect and dysmenorrhea, and the role of interpersonal relationships plays in this relationship. Methods The Cox Menstrual Symptom Scale (CMSS), short-form of Depression Anxiety Stress Scale, Interpersonal Comprehensive Diagnostic Scale and UCLA (University of California at Los Angeles) Loneliness Scale were applied to 855 adolescent nursing students to collect information on severity and frequency of dysmenorrheal symptoms, negative emotions (including depression, anxiety and stress), interpersonal problems and subjective experience of loneliness among them, and the relationship among these variables was examined. Results (1) Both the severity and frequency of dysmenorrhea were positively correlated with negative emotions, loneliness experience and interpersonal problems, while negatively correlated with age at menarche.(2) The negative emotions, romantic relationship and menarche age, but not loneliness and interpersonal problems, significantly contributed to both the severity and frequency of dysmenorrhea.(3) Mediation analysis revealed that the effects of loneliness and interpersonal problems on dysmenorrhea were totally mediated by negative emotions. Conclusions This investigation indicates that the relationship between interpersonal relationships and dysmenorrhea is mediated by negative emotions.

ACUPUNCTURE TREATMENT OF DYSMENORRHEA

Case HistoryPatient Wang, a female universitystudent aged 21 years, paid her first visit onAug. 16, 1990, with the chief complaint ofdysmenorrhea for one year. The patientcomplained that in the summer of 1989, oneday during her menstrual period when

The Analgesic Action of Semen Coicis on Severe Functional Dysmenorrhea—A Sequential Trial Observation

The analgesic effect of Semen Coicis was observed with the sequential trial in 26 cases of severe functional dysmenorrhea. The results showed that the markedly effective rate was 90%, which was much better than that of the control group treated by indomethacin plus subcutaneous injection of atropine (P≤0.01).

Effects of Acupressure and Ibuprofen on the Severity of Primary Dysmenorrhea

The present study aims at comparing the effects of acupressure using new combination of acupoints, and Ibuprofen on the severity of primary dysmenorrhea (PD). 216 female high school students, aged between 14 to 18 years, were randomly selected and divided into three groups. Each group underwent different treatment techniques: acupressure, Ibuprofen and sham acupressure as a placebo. The results indicated that the three therapeutic techniques were significantly effective in reducing the pain. However the therapeutic efficacies of acupressure and Ibuprofenwere similar with no significant difference, and were significantly better thanthe placebo. Thus acupressure, with no complications, is recommended as an alternative and also a better choice in the decrease of the severity of PD. ……

Prevalence of dysmenorrhea in female students in a Chinese university: a prospective study

This study aimed to investigate the prevalence of dysmenorrhea in a prospective approach. Menstruation-related diary data were obtained from 2640 female college students in North Sichuan Medical College;dysmenorrhea and related factors were analyzed. Dysmenorrhea occurred in 56.4% of students;6.5% of dysmenorrheal students suffered from “hard to bear” (unbearable) menstrual pain, and 6.5% had pre-menstrual dysmenorrhea. The more severe dysmenorrhea was, the longer dysmenorrhea lasted, and the longer the duration of menstruation and the larger the amount of menstrual blood flow appeared to be. Dysmenorrhea occurred on 37% of the menstrual dates on average and was unrelated to irregularity of menstrual cycles. The percentages of students taking medicine with mild, moderate and unbearable dysmenorrhea were 4.0%, 13.3% and 23.7%, respectively.

CLINICAL OBSERVATION ON 96 CASES OF PRIMARY DYSMENORRHEA TREATED BY MEDICINE-SEPARATED MOXIBUSTION AND INVESTIGATION ON ITS MECHANISMS

Objective： To observe the therapeutic effect of medicine-separated moxibustion for primary dysmenorrhea and its influence on plasma hormone level. Methods. Ninety-six patients suffering from primary dysmenorrhea were randomly and evenly divided into trealment group treated with medicine-separated moxibustion of Shenque （神阙 CV 8, 3-5 cones every time, beginning 1 week before onset of menstruation and stopping on the 3^rd day after onset, with 10 sessions being a therapeutic oourse, 3 courses all together）, and control group treated with oral administration of Yueyueshu （月月舒 menstruation-smoothing granule, 10 g/time, b.i.d, 3 courses altogether）. Menses prostaglandin E2（PGF2α） and plasma oxytocin （OT） during menstruation were determined by radioimmunoassay. Results; After the treatment, of the two 48 cases in treatment and control groups, 18 and 5 were cured, 24 and 9 had marked improvement in their symptoms, 6 and 26 had improvement, 0 and 8 failed in the treatment, with the total effective rates being 100. 096 and 83.3% respectively, the therapeutic effect of treatment group was markedly superior to that of control group （P〈0.05）. After the treatment, the contents of menses PGF2α in treatment group and plasma OT in both groups were significantly lower than those of pre-treatment （ P〈 0.01 ）. The therapeutic effect of moxibustion was significant- ly better than that of medication in lowering plasma OT. Conclusion： Medicine-separated moxibustion works well in treating primary dysmenorrhea, and moxibustion induced decrease of menses PGF2α and plasma OT may contribute to its effect in relieving dysmenorrhea.

Case Report of Surgical Excision of Non-Communicating Rudimentary Horn of Uterus Present in Adolescent with Dysmenorrhea

Unicornuate uterus with a rudimentary horn is a rare type of müllerian duct malformation. It leads to many obstetrical and gynecological complications. The mean age of presentation was the mid 20 s [1]. It is one of the differential diagnosis of dysmenorrhea in adolescent. A 19-year-old single was present with progressive severe dysmenorrhea and chronic pelvic pain after history right ovarian torsion treated by right salpinoophrectomy. Exploratory laparotomy was performed found unicornuate uterus with right non-communication rudimentary horn. Excised of right rudimentary horn was done. Remove of non-communication rudimentary horn will reduce symptoms of dysmenorrhea and chronic pelvic pain. Proper diagnosis and management will prevent misdiagnosis and good outcome to the patient.

EFFECT OF ACUPUNCTURE STIMULATION AT SANYINJIAO (SP 6) ON CEREBRAL GLUCOSE METABOLISM IN DYSMENORRHEA PATIENTS

To study the central mechanism of acupuncture stimulation of Sanyinjiao （三阴交 SP 6） in relieving dysmenorrhea. Methods： A total of 6 dysmenorrhea volunteer patients were subjected into this study. On the first positron emission tomography （PET） scan examination, they were assigned to pseudoacupuncture group by using the acupuncture needle just to prick the skin of Sanyinjiao （SP 6） ; while on the second PET scans, they were assigned to acupuncture group by inserting the needle into the same acupoint. 18F fluorodeoxyglucose （;SF-FDG） PET of the whole brain was performed during pseudo-acupuncture and real acupuncture of Sanyinjiao （SP 6）. The acquired PET data were analyzed by using statistical parametric mapping （SPM） software to determine changes of glucose metabolism in different cerebral regions. The patient＇s pain intensity was rated by using 0-10 numerical pain intensity scale. Results： After pseudo-acupuncture stimulation of Sanyinjiao （SP 6）, no significant changes were found in the pain intensity （ P 〉0.05）, while after real-acupuncture stimulation, the pain intensity declined significantly （ P〈0.01 ）. Following acupuncture of the right Sanyinjiao （SP 6）, multiple cerebral regions involving pain were activated （increase of glucose metabolism）, including ipsilateral lenticular nucleus （globus palliclus, putamen）, ipsilateral cerebellum and insular lobe, bilateral dorsal thalamus, ipsilateral paracentral Iobule, bilateral amygdaloid bodies, contralateral substantia nigra of the midbrain, bilateral second somatosensory （S Ⅱ ） areas, ispsilateral hippocampal gyms, frontal part of the ipsilateral cingulated gyrus, and bilateral mammary bodies of the hypothalamus. In addition, fewer regions of the cerebral cortex responded with decrease of the glucose metabolism after real acupuncture.

ACUPUNCTURE FOR PRI MARY DYSMENORRHEA──A meta-analysis

Recent literature search showed that up to now there are a total of 9 theses abo ut clinical treatment of primary dysmenorrhea with acupuncture therapy, among th em 5 clinical trials are from Chinese journals and the rest 4 from foreign journals. Majority of the tri als have some methodological and/or reporting shortcomings. The frequency and in tensity of dysmenorrhea are divided into intermittent and continuous types. Resu lts of quantitative meta-analysis with Revman 4.1 software showed that the exis t ing evidence supports the value of acupuncture for the treatment of dysmenorrhea . However, the quality of evidence is not fully convincing. There is an urgent n eed for well-planned, large-scale and multiple-center studies to assess the e ffe ctiveness and cost-effectiveness of acupuncture under real-life conditions.

ACUPUNCTURE TREATMENT OF 26 CASES OF PRIMARY DYSMENORRHEA

In the present paper, 26 cases of primary dysmenorrhea were treated with acupuncture at Guanyuan (CV 4), Zhongji (CV 3) and Sanyinjiao (SP 6). Results showed that after only two sessions of treatment, 16 cases were cured, 8 improved and 2 ineffective, with an effective rate of 92%.

AN ANALYSIS ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE AT SANYINJIAO POINT FOR TREATMENT OF 120 CASES OF PRIMARY DYSMENORRHEA

In the present paper, the authors make an analysis on the therapeutic effect of acupunc-ture at Sanyinjiao(SP 6) alone for treatment of 120 cases of primary dysmenorrhea. Results show atotal effective rate of 96.7%.