Head-to-Head Comparison of Electroacupuncture and Laser Acupuncture Effects on Autonomic Regulation and Clinical Effects in Dysmenorrhea: A Randomized Crossover Clinical Trial.

Introduction: Electroacupuncture (EA) has been applied in dysmenorrhea and has shown good efficacy. The mechanisms of EA are associated with autonomic nervous system adjustments and neuroendocrine regulation. Laser acupuncture (LA), however, has been widely investigated for its noninvasiveness. However, it remains uncertain whether LA is as effective as EA. This study aimed to compare EA and LA head to head in dysmenorrhea. Methods: A crossover, randomized clinical trial was conducted. EA or LA was applied to selected acupuncture points. Participants were randomized into two sequence treatment groups who received either EA or LA twice per week in luteal phase for 3 months followed by 2-month washout, then shifted to other groups (sequence 1: EA > LA; sequence 2: LA > EA). Outcome measures were heart rate variability (HRV), prostaglandins (PGs), pain, and quality-of-life (QoL) assessment (QoL-SF12). We also compared the effect of EA and LA in low and high LF/HF (low frequency/high frequency) status. Results: Totally, 43 participants completed all treatments. Both EA and LA significantly improved HRV activity and were effective in reducing pain (Visual Analog Scale [VAS]; EA: p < 0.001 and LA: p = 0.010) and improving QoL (SF12: EA: p < 0.001, LA, p = 0.017); although without intergroup difference. EA reduced PGs significantly (p < 0.001; δ p = 0.068). In low LF/HF, EA had stronger effects than LA in increasing parasympathetic tone in respect of percentage of successive RR intervals that differ by more than 50 ms (pNN50; p = 0.053) and very low-frequency band (VLF; p = 0.035). Conclusion: There is no significant difference between EA and LA in improving autonomic nervous system dysfunction, pain, and QoL in dysmenorrhea. EA is prominent in PGs changing and preserving vagus tone in low LF/HF; yet LA is noninvasive for those who have needle phobia. Whether LA is equivalent with EA and the mechanism warrants further study. Clinical trial identification number: NCT04178226.

Extracorporeal shock wave therapy for treating primary dysmenorrhea: A randomized controlled trial.

BACKGROUND: There are scanty data to apply radial extracorporeal shock wave therapy (rESWT) on the acupuncture points in the lower abdomen to reduce the menstrual pain. This trial aimed to test the rESWT safety and efficacy for treating primary dysmenorrhea (PD). METHODS: Forty-four young-women with PD were randomly assigned to one of the three groups: to receive rESWT on the acupuncture points during the follicular phase (Group A, n = 15) or during the luteal phase (Group B, n = 14), or to apply heat patch to the acupuncture points during the follicular phase as the control (Group C, n = 15) over three menstrual cycles. The pain severity (using 0-to-10 visual analog scale), the pain duration (hours), plasma PGF2α prostaglandin F2alpha and prostaglandin E2 (PGE2), self-rating anxiety scale and menstrual blood loss were assessed before and after interventions. RESULTS: The pain severity and duration significantly decreased in all groups after interventions. Although the reduced pain duration was not different among the groups, the reduced pain severity was more significant (P = .003) in Groups A (-53.8 ±â€Š33.7%) and B (-59.3 ±â€Š36.7%) than in Group C (-18.7 ±â€Š27.1%). The rESWT intervention did not change plasma prostaglandins in Group A, although there was a decreased prostaglandin F2alpha (-20.5 ±â€Š32.9%) in Group B or a decreased PGE2 (-18.9 ±â€Š17.8%) in Group C. The anxiety level showed no change after intervention. The menstrual blood volume reduced slightly after intervention and the change of menstrual blood loss in Group B was significant (P = .038). CONCLUSION: The rESWT applications on the abdominal acupuncture points safely and effectively reduced the menstrual pain, which was not associated with the prostaglandin changes. The rESWT-reduced pain seemed equally effective with the intervention applied during the follicular phase or luteal phase of the menstrual cycle. Heat patch placed on the abdominal acupuncture points also reduced the pain severity and duration, indicating that the improved blood flow could effectively alleviate the menstrual pain with PD. The changes in anxiety level and menstrual blood loss were slight after intervention.

The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis.

BACKGROUND: To our knowledge, data on the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis are limited. This study was conducted to determine the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 18-40 years old) with endometriosis. Participants were randomly allocated into two groups (30 participants each group) to receive either 50,000 IU vitamin D or placebo each 2 weeks for 12 weeks. RESULTS: Vitamin D supplementation significantly decreased pelvic pain (ß - 1.12; 95% CI, -2.1, -0.09; p=.03) and total-/HDL-cholesterol ratio (ß - 0.29; 95% CI, -0.57, -0.008; p=.04) compared with the placebo. Moreover, vitamin D intake led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (ß - 0.64 mg/L; 95% CI, -0.97, -0.30; p<.001) and a significant increase in total antioxidant capacity (TAC) (ß 47.54 mmol/L; 95% CI, 19.98, 75.11; p=.001) compared with the placebo. CONCLUSIONS: Overall, our study demonstrated that vitamin D intake in patients with endometriosis resulted in a significant improvement of pelvic pain, total-/HDL-cholesterol ratio, hs-CRP and TAC levels, but did not affect other clinical symptoms and metabolic profiles.

The Therapeutic Effect of Ge-Gen Decoction on a Rat Model of Primary Dysmenorrhea: Label-Free Quantitative Proteomics and Bioinformatic Analyses.

Ge-Gen decoction (GGD) is widely used for the treatment of primary dysmenorrhea (PD) in China. However, the mechanisms that underlie this effect are unclear. We investigated the protective mechanism of GGD in a rat model of PD using label-free quantitative proteomics. The model was established by the administration of estradiol benzoate and oxytocin. Thirty rats were divided into three groups (ten rats/group): a control group (normal rats), a model group (PD rats), and a treatment group (PD rats treated with GGD). The serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were measured by ELISA. Nanohigh-performance liquid chromatography-tandem mass spectrometry (nano-HPLC-MS/MS) was used to identify differentially expressed proteins (DEPs), and bioinformatics was used to investigate the protein function. Proteomic data were validated by western blot analysis. Oxytocin-induced writhing responses and abnormal serum levels of PGE2 and PGF2α were reversed following the administration of GGD. A total of 379 DEPs were identified; 276 were identified between the control group and the model group, 144 were identified between the model group and the treatment group, and 41 were identified as DEPs that were common to all groups. Bioinformatics revealed that the DEPs between the control group and the model group were mainly associated with cellular component biogenesis and binding processes. The DEPs between the model group and the treatment group were mainly involved in the protein binding and metabolic process. The expression levels of HSP90AB1 and the phosphorylation levels of ERK, JNK, and P-p38 in the uteri of rats in the three groups were consistent with the proteomic findings; MAP kinases (ERK, JNK, and p38) are known to be involved in the production of inflammatory cytokines and oxytocin signaling while HSP90AB1 is known to be associated with estrogen signaling. Collectively, these data indicate that GGD may exert its protective function on PD by regulating the inflammatory response and signaling pathways associated with oxytocin and estrogen.

Effect of traditional Chinese medicine formula GeGen decoction on primary dysmenorrhea: A randomized controlled trial study.

ETHNOPHARMACOLOGICAL RELEVANCE: GeGen Decoction, a well-known Chinese herbal formula, is widely used in China and other Asian countries to treat gynecological diseases, including primary dysmenorrhea. Pharmacological studies have confirmed that GeGen Decoction is able to inhibit spasmodic contractions of the uterus in vivo and in vitro. AIM OF THE STUDY: The objective of this study is to examine the efficacy and safety of GeGen Decoction on primary dysmenorrheic patients. METHODS: This was a randomized, double-blinded, placebo-controlled trial. GeGen Decoction or placebo was administered a week before the expected start of each cycle for three consecutive menstrual periods. Between-group differences in pain intensity were detected by visual analogue scale (VAS). In addition, serum levels of arginine vasopressin (AVP) and estrogen (E) were examined by enzyme-linked immunosorbent assay. Metabolomic analysis was further used to evaluate the influence of GeGen Decoction on the metabolomics of primary dysmenorrheic patients. RESULTS: A total of 71 primary dysmenorrheic women were recruited and 30 participants met the criteria were randomized into GeGen Decoction or placebo group. After three consecutive menstrual cycles' treatments, the VAS score of the GeGen Decoction group was significantly lower than that of the placebo group. Both serum levels of AVP and E decreased after GeGen Decoction administration, while the placebo seemed to have little effect on either of the index. Moreover, after GeGen Decoction treatment, seven important metabolites were identified by metabolomic analysis compared to the placebo group. No abnormalities in blood biochemical and routine physical examination pre and post GeGen Decoction intervention were observed. CONCLUSIONS: GeGen Decoction can remarkably relieve the severity of menstrual pain without obvious adverse effects. Its therapeutic effect on primary dysmenorrhea might be related to the regulation of pituitary hypothalamic ovarian hormones, and interfering with the metabolic change.

Clinical trial for the management dysmenorrhea using selected spices.

BACKGROUND: Dysmenorrhea is the most common gynecologic complaint among adolescent and adult females. Some dysmenorrheic females do not respond to treatment with NSAIDs or oral contraceptives and exhibit contraindications to such medications. Therefore, alternative medication gained importance in management of dysmenorrhea. METHODS: A comparative clinical trial was conducted on thirty-one dysmenorrheic subjects, who were randomly assigned to three groups. The dosage was 1gr/day, 3gr/day and 3gr/day for Ginger, Dill seeds, and Cumin, respectively. The girls in respective group consumed the spice for three days during each cycle for three consecutive cycles. RESULTS: Dill seed was effective in reducing pain, followed by ginger wherein Cumin did not exhibit any effect. Cumin exhibited significant reduction in systemic responses like cold sweats, backache, fatigue and cramps. CONCLUSION: Dill seeds were more effective in reducing pain. It was obvious from our study that reducing symptoms is also important in the overall management of dysmenorrhea.

Investigating the effect of Eye Movement Desensitization and Reprocessing on pain intensity in patients with primary dysmenorrhea: a protocol for a randomized controlled trial.

BACKGROUND: Unpleasant experience with the previous menstruation can increase the sensitivity to pain which may lead to moderate to severe pain in patients with dysmenorrhea. Eye movement desensitization and reprocessing (EMDR) is a psychological method to alleviate the distress from unpleasant memories and related events and can be used for other conditions such as anxiety, depression, and chronic pain. This protocol was designed to investigate the effect of EMDR therapy on pain intensity in patients with dysmenorrhea. METHODS/DESIGN: A randomized clinical trial was designed in compliance with the Consolidated Standards of Reporting Trials (CONSORT). Female students who have moderate to severe primary dysmenorrhea (based on a visual analogue scale [VAS] score of at least 4 for two consecutive months) and who live in dormitories at Qazvin University of Medical Sciences in Qazvin, Iran will be invited to participate in the study. The total sample size will be 88 girls, who will be randomly assigned to intervention (N = 44) and control (N = 44) groups. EMDR therapy will be performed for the intervention group, while the control group can use sedative or other pain relife methods as their routin... There will be six treatment sessions, which will be held twice a week. The duration of each session is 30-90 min, according to the convenience of each participant. The data will be collected using the demographic characteristics questionnaire, the VAS, the Subjective Units of Anxiety or Distress Scale (SUD), and the Validity of Cognition Scale (VOC). The data on pain intensity due to primary dysmenorrhea in both groups will be collected at 1 and 2 months before the intervention (to identify eligible participants) and 1 and 2 months after the intervention (follow-ups). Data will be analyzed by using SPSS version 25 software and analysis of variance (ANOVA) with repeated measures with appropriate post hoc tests. A P value of less than 0.05 will be considered significant. DISCUSSION: The results are expected to provide the information on the efficacy of EMDR therapy to manage moderate to severe pain in patients with primary dysmenorrhea. ETHICS AND DISSEMINATION: The research proposal is approved by the human ethics committee of Qazvin University of Medical Sciences (IR.QUMS.REC.1397.100). The results of this trial will be submitted for publication in a peer-reviewed research journal. TRIAL REGISTRATION: IRCT20180823040851N1 . Registered on 6, October 2018.

Personal perception and body awareness of dysmenorrhea and the effects of rhythmical massage therapy and heart rate variability biofeedback-A qualitative study in the context of a randomized controlled trail.

OBJECTIVE: The purpose was to involve women's personal experiences of daily life with primary dysmenorrhea (PD) and their body perceptions of the dysmenorrhea-related symptoms in relation to the treatment procedure and to explore the perception of Heart Rate Variability Biofeedback (HRV-BF) or Rhythmical Massage (RM) according to Ita Wegman as a therapeutic intervention within the framework of Anthroposophic Medicine (AM). DESIGN: From 60 women who participated in our randomized controlled trial analyzing the effects of HRV-BF or RM, we examined 14 women to get an in-depth understanding of this prevalent disease, using a qualitative design. The women drew their body image before and after the 3-month-intervention on body silhouette diagrams and described their body-perceptions. Semi-structured interviews were conducted and analyzed using content analysis. RESULTS: Women perceive dysmenorrhea as a disturbance of their daily lives. The body images showed the variations of experience, from misbalances of body perception to overwhelming attacks of pain hindering a normal life for several days per month. Perception of therapeutic interventions range from relaxing without effects on complaints to important changes and benefits on the physical, emotional, and/or social level. Both therapies can support stronger self-awareness through enabling a more differentiated sense of body-awareness, sometimes resulting in women experiencing fewer limitations in their daily lives. Effects may be influenced by the readiness to resonate with the therapeutic process. Qualitative interviews and body images can serve as tools to integrate individuality and help to integrate embodied more or less conscious aspects of complaints. CONCLUSIONS: The body silhouette diagram could be used systematically to include reflections of embodiment in the therapeutic and research settings and help to diagnose in advance the ability of participants to resonate with interventions. RM and HRV-BF influence self-awareness and may enable salutogenic and self-management capacities. For more effective treatment it may be helpful to make treatment suggestions based on an integrative individual history that includes preferences, expectations and a body silhouette diagram.

Influence of the quickness and duration of De Qi on the analgesic effect of acupuncture in primary dysmenorrhea patients with a cold and dampness stagnation pattern.

OBJECTIVE: To investigate the influence of the quickness and duration of De Qi (or Qi arrival) on the analgesic effect of acupuncture in primary dysmenorrhea patients with a cold and dampness stagnation pattern. METHODS: Sixty-eight patients were randomly assigned to the De Qi group (deep needling with thick needles and manipulation, n = 17) or the non-De Qi group (shallow needling with thin needles and no manipulation, n = 51). Both groups underwent needling at Sanyinjiao (SP 6) for 30 min. The visual analogue scale was used to measure the degree of menstrual pain, and the Acupuncture De Qi Clinical Assessment Scale was used to assess De Qi. Only data from patients who experienced actual De Qi were included in the analysis. RESULTS: Thirty-nine patients experienced actual De Qi. Patients who experienced actual De Qi in the De Qi group (n = 14) felt De Qi more rapidly (P = 0.028) and for a longer duration (P = 0.04) than patients who experienced actual De Qi in the non-De Qi group (n = 25). Both groups showed a reduction in the visual analogue scale score for pain after treatment. The analgesic effect did not significantly differ between the two groups. The occurrence time of De Qi showed a significant negative correlation with pain reduction at 20 and 30 min after needle removal (P < 0.05). There was no correlation between the duration of De Qi and the therapeutic effect. CONCLUSION: In primary dysmenorrhea patients with a cold and dampness stagnation pattern, quicker onset of De Qi when needling Sanyinjiao (SP 6) achieves a better analgesic outcome. However, a longer duration of De Qi does not affect the degree of analgesia. Compared with minimal acupuncture, active acupuncture stimulation achieves a more rapid onset and longer duration of De Qi.

Scientific and technological prospection on transdermal formulations and complementary therapies for the treatment of primary dysmenorrhea.

INTRODUCTION: Primary dysmenorrhea (PD) is another term for idiopathic menstrual cramps. Treatments include the use of oral non-steroidal anti-inflammatory drugs (NSAIDs). These drugs have several side effects. The objective of this study was to perform a systematic review on the transdermal administration of drugs and the use of alternative therapies for the treatment of PD. AREAS COVERED: The article bases were Web of Science, PubMed and Sciencedirect and the patent bases were INPI, EPO and WIPO with publications on Primary Dysmenorrhea and associations with Transdermal Administration; Complementary Therapies and Medicinal Plants. 21 articles and 12 patents were analyzed. The results demonstrate the need for alternative therapies for the treatment of PD, with greater effectiveness and lower side effects, mainly in an attempt to reduce the intensity and duration of pain as well as reducing the continuous use of medications. EXPERT OPINION: The study of technological prospection highlighted the relevant importance in seeking new methods for the relief of the symptoms provoked by this condition. The perspectives coexist in the discovery of new natural and biotechnological pharmacological applications, mainly in the development of new devices capable of facilitating and optimizing this form of administration in an attempt to reduce side effects.

Comparative efficacy and safety of NSAIDs-controlled acupuncture in the treatment of patients with primary dysmenorrhoea: a Bayesian network meta-analysis.

BACKGROUND: Acupuncture and non-steroidal anti-inflammatory drugs (NSAIDs) are used frequently to treat primary dysmenorrhoea. However, it is unclear whether this treatment greatly reduces the risk of primary dysmenorrhoea. METHODS: Eight databases were searched up to January 2018. Pair-wise and network meta-analyses were conducted to synthesize data from eligible studies. RESULTS: Seventeen randomized controlled trials were included. The following acupuncture types showed more efficacy than NSAIDs in reducing primary dysmenorrhoea risk: traditional acupuncture (odds ratio [OR] = 6.70, 95% confidence interval [CI] 2.60-20.0), eye acupuncture (OR = 3.50, 95% CI 1.40-8.90), wrist-ankle acupuncture (OR = 6.00, 95% CI 1.30-32.0), superficial acupuncture (OR= 5.10, 95% CI 1.20-26.0), moxibustion (OR = 7.70, 95% CI 2.90-25.0), electroacupuncture (OR = 23.0, 95% CI 4.80-130), ear acupuncture (OR = 13.0, 95% CI 2.80-100) and abdominal acupuncture (OR = 5.30, 95% CI 2.10-16.0). Surface under the cumulative ranking curve values were traditional acupuncture (53.0%), eye acupuncture (22.0%), wrist-ankle acupuncture (81.5%), superficial acupuncture (50.0%), moxibustion (57.8%), electroacupuncture (99.9%), ear acupuncture (41.6%) and abdominal acupuncture (44.1%). CONCLUSION: Acupuncture is more efficacious than NSAIDs in reducing primary dysmenorrhoea risk. Acupuncture, particularly electroacupuncture, can decrease the risk of primary dysmenorrhoea.

A randomized comparative study of herbal decoction of Cassia fistula Linn pod's pericarp and Myristica fragrans Houtt arils vs. mefenamic acid in spasmodic dysmenorrhoea.

Background To compare the efficacy and safety of herbal decoction (pods of Cassia fistula Linn. and Arils of Myristica fragrans Houtt) with mefenamic acid in spasmodic dysmenorrhoea. Methods In this single-blind, prospective, parallel, standard controlled study, dysmenorrheic patients (n=64) were randomly allocated to receive herbal decoction (n=31) or mefenamic acid (n=33) for two consecutive menstrual cycles. Treatment group received 180 mL herbal decoction of post amaltas (Cassia fistula L pod's pericarp) (21 g), bisbasah (Myristica fragrans Houtt arils) (3 g) and qand siyah (jaggery) (30 g) which were orally administered at morning for 3 days before the expected start of menstruation. The control group received mefenamic acid 500 mg orally twice daily between day 1 and day 3 of menstruation. The primary outcomes were visual analog scale (VAS) for pain intensity, pain relief scale and the safety assessment by clinical examination and biochemical parameters. The secondary outcomes included health-related quality of life (HRQoL) determined by SF-12 health survey questionnaire, duration of pain and pictorial blood assessment chart score for menstrual blood loss. The data were statistically interpreted with 5% level of significance. Results At the baseline, on day 1, pain severity for VAS score between the groups [7.09 ± 1.07 vs. 6.75 ± 1.09] had no significant difference (p>0.05). However, during the second menstrual cycle, a significant reduction [0.03 + 0.17 vs. 0.42 + 1.44] in pain severity on day 1 was noted in both groups (p<0.001). During the second menstrual cycle, improvement in HRQoL health survey [SF-12 total score: 85.88 ± 5.99 vs 74.83 ± 15.9] and reduction in pain duration were significantly higher in the treatment group compared to the control group. No side effects were reported. Conclusion Herbal decoction was effective to relieve pain and to improve HRQoL in spasmodic dysmenorrhoea.

Acupoint herbal plaster for patients with primary dysmenorrhea: study protocol for a randomized controlled trial.

BACKGROUND: Primary dysmenorrhea (PD), is one of main gynecological complaints in women of child-bearing age. Common medications for PD do not always achieve satisfactory outcome of pain relief. Hence, both health professionals and patients are seeking help from complementary and alternative medicine. The acupoint herbal plaster (AHP), which appears to be a safe and effective way to alleviate menstrual pain, as well as to improve other PD-related symptoms. Despite similar clinical studies for this condition in the past, no high-quality methodology-based clinical trial has been reported to date. The current study aims to assess the efficacy of the AHP compared with the acupoint placebo plaster (APP) and being placed on a waiting-list control group in patients with primary dysmenorrhea. METHODS/DESIGN: This study is a randomized, single-center, placebo-controlled clinical trial. A total of 180 women with PD will be included and randomly allocated to the AHP, APP and waiting-list (WL) groups in a 1:1:1 ratio. Patients in the AHP group will be provided with herbal plasters (Shaofuzhuyu decoction) on various acupoints: Shenque (CV8), Guanyuan (CV4), Qihai (CV5), Ciliao (BL32) and Zigong (EX-CA1). Women in the APP group will receive placebo plasters on the same acupoints, and no intervention will be given to the WL group until completion of the study. The primary outcome will be pain intensity reduction measured by a Visual Analog Scale (VAS), with other outcome measurements including the Cox Menstrual Symptom Scale (CMSS), the 12-Item Short Form Health Survey (SF-12) and the Participant Global Impression of Change (PGIC). All assessments will be performed at baseline, each menstrual cycle during the treatment course and the follow-up course. Any adverse events will be recorded throughout the study. DISCUSSION: This is the first study to compare the changes in menstrual pain after three different interventions: the active intervention (AHP), the placebo intervention (APP), and a period of no intervention (WL). This three-arm randomized controlled trial (RCT) aims to investigate the relative contributions of the specific (AHP vs. APP) and non-specific (APP vs. WL) effects to the overall clinical effects of the active AHP on women with PDM. The scientific and rigorous methodology design of this trial should gather good evidence to assess the curative effects and safety of the AHP on PD. Moreover, the results of this study may provide evidence-based references for the treatment of menstrual pain in future. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-TRC-16008701. Registered on 22 July 2016.

Extracts of compound Muniziqi granule suppressed uterus contraction and ameliorated oxytocin-induced primary dysmenorrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Muniziqi granule (CMG) is usually used as a traditional Uighur medicine to treat acne, chloasma, skin inflammation, primary dysmenorrhea (PDM), and menopausal syndrome. However, there are no sufficient data to support the clinic uses of CMG in PDM. AIM OF THE STUDY: This work aims to examine the effect of CMG as a treatment for PDM and reveal its possible therapeutic mechanism. MATERIALS AND METHODS: In vivo and in vitro mouse PDM models were utilized in this study. The mouse uterine contraction was induced by oxytocin after progynova or estradiol benzoate pretreatment. CMG, alkaloid extracts from seeds of Peganum harmala (AEP), and 10% and 95% ethanol extracts from seeds of Nigella glandulifera (EEN10 and EEN95) were given to mice in three doses by gavage. The writhing times within 30 min after oxytocin treatment were recorded to evaluate the analgesic effect, and the glutathione peroxidase (GSH-Px), malondialdehyde (MDA), 6-keto-prostaglandin F1α (6-k-PGF1α), prostaglandin F2α (PGF2α), thromboxane B2 (TXB2), and nitric oxide (NO) levels in uterine tissues and PGF2α and MDA in serum were determined. The effects (contractile curve) of CMG, AEP, EEN10, and EEN95 on uterus contraction induced by oxytocin in isolated mouse uterus were recorded. RESULTS: In contrast to the control group, CMG, AEP, N10, and N95 could display analgesic activities dose dependently by reducing the writhing response of the PDM model mice. CMG, AEP, EEN10, and EEN95 could also remarkably decrease the level of PGF2α, 6-k-PGF1α, TXB2, NO and MDA in uterine tissues and PGF2α and MDA in serum, whereas the activity of GSH-Px in uterine tissues was increased. Furthermore, CMG, AEP, EEN10, and EEN95 could significantly inhibit the frequency and amplitude of isolated uterus induced by oxytocin in a concentration-dependent manner. CONCLUSIONS: CMG exhibited a significant protective effect on experimental PDM. The mechanisms are probably associated with abating lipid peroxidation and over-inflammatory reaction, and alleviating the contraction of isolated mouse uterus. The seeds of P. harmala and N. glandulifera in the CMG may play an important role in exerting protective effects on PDM. This study provides pre-clinic proof to the use of CMG in clinical practice of PDM.

Intensity Dependence of Auditory Evoked Potentials in Primary Dysmenorrhea.

Some studies suggest that women with primary dysmenorrhea have distinct emotional or personality features. For example, they might exaggerate their responses to external stimuli, such as to intensity-increasing auditory stimuli. Fifteen women with primary dysmenorrhea and 15 healthy women were invited to undergo tests of the intensity dependence of auditory evoked potentials (IDAEP), the Functional and Emotional Measure of Dysmenorrhea, and the Plutchik-van Praag Depression Inventory. Study participants with dysmenorrhea showed higher Functional and Emotional scale scores and stronger IDAEP. Regarding the IDAEP generation, the source inversion of N1 and P2 disclosed the activated bilateral superior temporal gyri, medial and superior prefrontal gyri in all participants, and additionally, the middle frontal gyri in dysmenorrhea patients. We report a pronounced IDAEP in primary dysmenorrhea, which indicates the decreased cerebral serotonergic innervations and points to increased activations in the prefrontal and frontal areas in the disorder. PERSPECTIVE: Using an IDAEP technique, the authors found decreased serotonergic innervation and altered cerebral activation in women with primary dysmenorrhea, which might offer some pharmacotherapeutic clues for the disorder.

Comparative study on skin temperature response to menstruation at acupuncture points in healthy volunteers and primary dysmenorrhea patients.

OBJECTIVE: To assess skin temperature response to menstruation at acupuncture points in primary dysmenorrhea (PD) patients and healthy volunteers so as to explore acupuncture point specificity in reflecting diseases in the light of skin temperature. METHODS: Fifty-two PD patients and 49 healthy volunteers were recruited. Skin temperature measurements were performed with a skin temperature assessment device at 10 points. Absolute difference between skin temperature of the same point on the left and right side is used as main outcome measure. RESULTS: On the first day of menstruation, when menstrual pain attacking in PD patients, a significant increase in skin temperature difference was detected at Taixi (KI 3) compared with the healthy group (P < 0.01). A significant reduction in skin temperature difference was detected at Taixi (KI 3) in the first day of menstruation compared with those values in the third day after menstruation (P < 0.01) in the healthy group. On the third day after menstruation, a significant reduction in skin temperature difference was found at Zhongdu (LR 6) in PD group compared with the healthy group (P < 0.05). No significant differences of skin temperature were detected at other points (P > 0.05). CONCLUSION: The skin temperature difference at menstruation-relevant points in PD patients did not all change significantly more than those in women without PD. Significant difference was only found in Taixi (KI 3), the Yuan-source point of Kidney meridian.

Traditional Chinese medicine Guizhi Fuling capsule used for therapy of dysmenorrhea via attenuating uterus contraction.

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling formula, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, is composed of Cinnamomum cassia (L.) J.Presl (Cassia bark), Poria cocos (Schw.) Wolf (Poria), Paeonia suffruticosa andrews (Moutan Cortex), Paeonia lactiflora Pall (Herbaceous peony), and Amygdalus persica L.(Persicae Semen). It has clinical efficacy of activating blood circulation to dissipate blood stasis and is commonly used for the treatment of primary dysmenorrhea. However, its therapeutic mechanism has not been clearly elucidated. The aim of this study is to reveal molecular mechanisms of action using in vivo and in vitro experimental models. MATERIAL AND METHODS: The ICR mouse uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment. Mice were given GZFLC (0.54, 1.08g/kg) by gavage. The levels of NO, PGF2α and Ca(2+) in uterine tissue were determined according to instructions. Cyclooxygenase-2 (COX-2) and oxytocin receptor (OTR) proteins in uterine tissue were assessed by Western Blot. Mouse isolated uterus strips were mounted in tissue organ baths containing Locke's solution. The contractile responses were recorded with Power Lab recording system. The effect of GZFLC on spontaneous uterine contraction, and uterine contraction induced by oxytocin, PGF2α was observed. Myometrial cells were exposed to oxytocin (5U/L) to induce calcium release, and the effect of GZFLC and its components (PL, PGG, CA) on intracellular Ca(2+) was analyzed with fluorometry imaging. RESULTS: In vivo study demonstrated that GZFLC significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 55%. It also decreased the levels of NO, PGF2α and Ca(2+) in oxytocin-induced mice uterine tissue. Moreover, Western blot analysis showed that COX-2 and OTR expressions in uterine tissue of dysmenorrhea mice were significantly reduced. GZFLC inhibited spontaneous uterus contractions in a dose-dependent manner, and the IC50 value was 0.99mg/ml. The IC50 values of GZFLC on PGF2α, oxytocin-induced contractions were 1.45mg/ml, 3.53mg/ml, respectively. Further in vitro studies indicated that GZFLC and its components (PL, PGG, CA) could restrain intracellular calcium levels in favour of uteri relaxation. CONCLUSIONS: Both in vivo and in vitro results indicated that GZFLC possessed a significant spasmolytic effect on uterine tetanic contraction. The present study provides in vivo and in vitro experimental evidence to support the use of GZFLC for the clinical treatment of primary dysmenorrheal (PD).

Ge-Gen Decoction attenuates oxytocin-induced uterine contraction and writhing response: potential application in primary dysmenorrhea therapy.

The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea (PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction (GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F2 alpha (PGF2α) and Ca(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF2α and Ca(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.

Comparison the effect of mefenamic acid and Teucrium polium on the severity and systemic symptoms of dysmenorrhea.

BACKGROUND: Primary dysmenorrhea is a prevalent problem and its effects decrease the quality of life in many women across the world. The aim of this study was to research the effect of Teucrium polium compared to mefenamic acid on primary dysmenorrhea. MATERIALS AND METHODS: This triple-blind, randomized, clinical trial study was performed on 70 single female students between 20 and 30 years old educating in Shahid Beheshti University (Tehran, Iran) from October 2014 to February 2014.They were allocated randomly into two groups: In T. polium group (n = 35) who took 250 mg of T. polium powder q6h for the first 3 days of menstruation for two cycles. The second group (n = 35) received 250 mg mefenamic acid,. Dysmenorrhea severity was determined by visual analog scale (VAS). RESULTS: There were no differences between two groups for demographic or descriptive variables. Comprising the VAS showed that the participants in T. polium and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after the treatment (P < 0.05). No side effects were reported in the T. polium and Mefenamic Acid groups. CONCLUSION: T. polium was as effective as mefenamic acid in decreasing the pain severity in primary dysmenorrhea.

[Effect of drug-spreading moxibustion for primary dysmenorrheal with cold-damp stagnation and its uterine artery blood flow].

OBJECTIVE: To observe the effect difference between drug-spreading moxibustion and the oral administration of meloxicam for primary dysmenorrheal with cold stagnation and to explore its mechanism. METHODS: A total of 101 patients with primary dysmenorrheal were randomly assigned into a drug-moxibustion group(52 cases) and a western medication group(49 cases). Drug-spreading moxibustion was used on the lumbosacral acupoints area and then around lower abdominal five days before menstruation until the 3rd day of menstruation,once three days,while western medicine meloxicam was prescribed one day before menstruation,7.5 mg at a time,once a day and continuously for three days. The clinical effects after one course,namely three menstrual cycles,were compared between the two groups. Meanwhile,the resistance index(RI) and the pulsatility index (PI) of uterine artery and arcus arteriarum were examined through color Doppler ultrasound before and after treatment. RESULTS: After one-course treatment,the effective rate was 92.3%(48/52) in the drug-spreading moxibustion group,which was better than 67.3%(33/49) in the western medication group(P<0.05). Also,all the RI and PI in the drug-spreading moxibustion group were obviously decreased than those before treatment(all P<0.05),and the ones were superior to those of the western medication group(all P<0.05),which showed no apparent decrease after treatment(all P>0.05). CONCLUSIONS: Drug-spreading moxibustion can improve the symptoms of primary dysmenorrheal with cold-damp stagnation,and the effect is better than that of meloxicam. The mechanism may be related to improve the blood supply to the uterus.