An integrated study of metabolomics and transcriptomics to reveal the anti-primary dysmenorrhea mechanism of Akebiae Fructus.

ETHNOPHARMACOLOGICAL RELEVANCE: Akebiae Fructus, a Tujia minority folk medicine and a well-known traditional Chinese medicine for soothing the liver, regulating Qi, promoting blood circulation and relieving pain, is widely used in the treatment of primary dysmenorrhea. However, little is known about its underlying mechanism. AIM OF THE STUDY: To explore the effect of Akebiae Fructus on primary dysmenorrhea model induced by estradiol benzoate and oxytocin, and to provide better understanding of the mechanism of Akebiae Fructus for primary dysmenorrhea treatment. MATERIALS AND METHODS: The primary dysmenorrhea mouse model was used in this study. Except for the control group and the normal administration group, the mice of other groups were subcutaneously injected with estradiol benzoate (10 mg/kg/d) for 10 consecutive days. From the 5th day of the ten-day model period, the positive control groups were given 0.075 g/kg ibuprofen and 7.5 g/kg Leonurus granule, the drug groups were given 0.2 g/kg, 0.4 g/kg, 0.8 g/kg Akebiae Fructus extract, the normal administration group was given 0.8 g/kg Akebiae Fructus extract, and the same volume saline was given in the control group. On the tenth day, oxytocin (10 U/kg) was peritoneally injected after estradiol benzoate injected 1 h. After the oxytocin injection, writhing behavior was observed for 30 min. Then the uterine tissue was collected to measure the level of PGF2α and PGE2, and for histological analysis and transcriptomics analysis. Meanwhile, plasma and urine samples were collected for metabolomic analysis. RESULTS: Akebiae Fructus inhibited the writhing, decreased the PGF2α level and ameliorated the morphological changes. 32 potential metabolic biomarkers in plasma and 17 in urine were found for primary dysmenorrhea, and after Akebiae Fructus treatment, 25 metabolites in plasma and 14 in urine were restored. These altered metabolites were mainly involved in lipid, amino acid and organic acid metabolism. For the transcriptomic study, a total of 2244 differentially expressed genes (1346 up-regulated and 898 down-regulated) were obtained between the control and model group, and 148 differentially expressed genes (DEGs) were found related with Akebiae Fructus treatment of primary dysmenorrhea. Correlation analysis was carried out based on the transcriptomic and metabolomic data. 5 differentially expressed genes (Plpp3, Sgpp2, Arg1, Adcy8, Ak5) were found related with the enrichment metabolic pathways. The mechanism by which Akebiae Fructus ameliorates primary dysmenorrhea may account for the regulation of the gene expression to control the key enzymes in the sphingolipid metabolism, arginine and proline metabolism, glycerophospholipid metabolism and purine metabolism, inhibiting the abnormal secretion of PGF2α, alleviating the uterine contraction and reducing inflammation and pain. CONCLUSIONS: Akebiae Fructus could effectively alleviate the symptoms of primary dysmenorrhea, regulate metabolic disorders, and control the related gene expression in primary dysmenorrhea. The study may provide clues for further study of Akebiae Fructus treatment on primary dysmenorrhea.

The Relationship between Serum Ischemia-Modified Albumin Levels and Uterine Artery Doppler Parameters in Patients with Primary Dysmenorrhea.

OBJECTIVE: Primary dysmenorrhea occurs due to abnormal levels of prostanoids, uterine contractions, and uterine blood flow. However, the reasons for pain in primary dysmenorrhea have not yet been clarified. We examined the blood flow alterations in patients with primary dysmenorrhea and determined the relationship between ischemia-modified albumin (IMA) levels, as an ischemia indicator, and primary dysmenorrhea. METHODS: In the present study, 37 patients who had primary dysmenorrhea and were in their luteal and menstrual phase of their menstrual cycles were included. Thirty individuals who had similar demographic characteristics, who were between 18 and 30 years old and did not have gynecologic disease were included as control individuals. Their uterine artery Doppler indices and serum IMA levels were measured. RESULTS: Menstrual phase plasma IMA levels were significantly higher than luteal phase IMA levels, both in the patient and in the control groups (p < 0.001). Although the menstrual phase IMA levels of patients were significantly higher than those of controls, luteal phase IMA levels were not significantly different between the two groups. Menstrual uterine artery pulsatility index (PI) and resistance index (RI) of primary dysmenorrhea patients were significantly different when compared with luteal uterine artery PI and RI levels. There was a positive correlation between menstrual phase IMA and uterine artery PI and RI in the primary dysmenorrhea. CONCLUSION: Ischemia plays an important role in the etiology of the pain, which is frequently observed in patients with primary dysmenorrhea. Ischemia-modified albumin levels are considered as an efficient marker to determine the severity of pain and to indicate ischemia in primary dysmenorrhea.

The relationship between serum ischemia-modified albumin levels and uterine artery doppler parameters in patients with primary dysmenorrhea

Abstract Objective Primary dysmenorrhea occurs due to abnormal levels of prostanoids, uterine contractions, and uterine blood flow. However, the reasons for pain in primary dysmenorrhea have not yet been clarified. We examined the blood flow alterations in patients with primary dysmenorrhea and determined the relationship between ischemia-modified albumin (IMA) levels, as an ischemia indicator, and primary dysmenorrhea. Methods In the present study, 37 patients who had primary dysmenorrhea and were in their luteal and menstrual phase of their menstrual cycles were included. Thirty individuals who had similar demographic characteristics, who were between 18 and 30 years old and did not have gynecologic disease were included as control individuals. Their uterine artery Doppler indices and serum IMA levels were measured. Results Menstrual phase plasma IMA levels were significantly higher than luteal phase IMA levels, both in the patient and in the control groups (p < 0.001). Although the menstrual phase IMA levels of patients were significantly higher than those of controls, luteal phase IMA levels were not significantly different between the two groups. Menstrual uterine artery pulsatility index (PI) and resistance index (RI) of primary dysmenorrhea patients were significantly different when compared with luteal uterine artery PI and RI levels. There was a positive correlation between menstrual phase IMA and uterine artery PI and RI in the primary dysmenorrhea. Conclusion Ischemia plays an important role in the etiology of the pain, which is frequently observed in patients with primary dysmenorrhea. Ischemia-modified albumin levels are considered as an efficient marker to determine the severity of pain and to indicate ischemia in primary dysmenorrhea.

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.

Low Serum Oxytocin Concentrations Are Associated with Painful Menstruation.

Oxytocin-dependent mechanisms are hypothesized to contribute to painful menses, but clinical trials of oxytocin antagonists for dysmenorrhea have had divergent outcomes. In contrast, broader studies have shown that increased systemic oxytocin concentrations are associated with increased pain tolerance and improved psychosocial function. We sought to confirm whether increased serum oxytocin concentrations are associated with menstrual pain and other psychosocial factors. Women with a history of primary dysmenorrhea (n = 19), secondary dysmenorrhea (n = 12), and healthy controls (n = 15) completed pain and psychosocial questionnaires, provided a medical history, and rated their pain during the first 48 h of menses. Serum samples were collected during menses to measure oxytocin concentrations. Oxytocin was significantly lower in participants with a history of primary (704 ± 33 pg/mL; p < 0.001) or secondary (711 ± 66 pg/mL; p < 0.01) dysmenorrhea compared to healthy controls (967 ± 53 pg/mL). Menstrual pain over the past 3 months (r = -0.58; p < 0.001) and during the study visit (r = -0.45; p = 0.002) was negatively correlated with oxytocin concentrations. Pain catastrophizing (r = -0.39), pain behavior (r = -0.32), and pain interference (r = -0.31) were also negatively correlated with oxytocin levels (p's < 0.05). Oxytocin was not significantly correlated with psychosocial factors. Contrary to our hypothesis, women with a history of primary or secondary dysmenorrhea had lower oxytocin concentrations during menses when compared to healthy controls. Lower circulating oxytocin concentrations were also associated with worse menstrual pain and pain-related behavior. When considering the existing literature, low circulating oxytocin may be a sign of dysfunctional endogenous pain modulation.

Comparative pharmacokinetics study of leonurine and stachydrine in normal rats and rats with cold-stagnation and blood-stasis primary dysmenorrhoea after the administration of Leonurus japonicus houtt electuary.

Leonurus japonicus houtt, a well-known herb of traditional Chinese medicine, is widely used to treat gynaecological diseases. In this study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method for simultaneously quantifying leonurine and stachydrine, the two main bioactive components in Leonurus japonicus houtt, was developed and validated. Plasma samples were prepared by protein precipitation with acetonitrile and separation by a Hewlett Packard XDB-C8 column (150 × 4.6 mm, id, 5 µm) equipped with a gradient elution system containing methanol-water and 0.1% formic acid at a flow-rate of 0.4 mL/min. Components were then detected by a mass spectrometer in positive electrospray ionization mode. This method showed good linearity, precision, accuracy, recovery, stability, and negligible matrix effects, which were within acceptable ranges. The method was successfully applied to compare the pharmacokinetics in normal rats and rats with cold-stagnation and blood-stasis primary dysmenorrhoea treated with Leonurus japonicus houtt electuary. The result showed significant differences (p < 0.05) in the pharmacokinetic parameters between the primary dysmenorrhoea and normal groups. This result implied that Leonurus japonicus houtt electuary remained longer and was absorbed slower in rats with primary dysmenorrhoea and exhibited higher bioavailability and peak concentration.

Markers of lipid and protein peroxidation among Nigerian university students with dysmenorrhea.

INTRODUCTION: Oxidative stress has been associated with primary dysmenorrhea, but studies that have assessed multiple markers of peroxidation are scarce. This study investigated malondialdehyde (MDA), nitrotyrosine (3-NT), and protein carbonyls (PrCarb) as markers of oxidative stress and antioxidant status by serum alpha tocopherol level in young Nigerian women with dysmenorrhea. MATERIALS AND METHODS: In a case-control design, 45 female undergraduates who had had regular menses for at least six previous cycles were recruited consecutively from a university clinic as cases and 45 apparently healthy age-matched counterparts in their hall of residences as controls. Serum levels of MDA, 3-NT, and PrCarb were determined using standard methods, and the values were compared between cases and controls using Mann-Whitney U-test and graphs. RESULTS: Study participants' ages range from 16 to 29 years (mean = 22.0 ± 3.1 years). Serum level of 3-NT (45.89 ± 37.11 vs 21.27 ± 13.94 ng/mL) and MDA (0.75 ± 0.19 vs 0.45 ± 0.11 nmol/mL) was significantly higher in cases than controls. Plasma alpha tocopherol was significantly lower in cases (7.51 ± 1.95 µmol/L) than controls (8.98 ± 1.95 µmol/L). Conversely, PrCarb levels were not significantly difference between cases and controls. There were significant correlations between alpha tocopherol and 3-NT (r = -0.285; P = 0.007) and MDA (r = -0.321; P = 0.002), whereas this relationship was not shown with PrCarb (r = -0.073; P = 0.496). CONCLUSION: Remarkable lipid and protein peroxidation observed in young Nigerian women with dysmenorrhea was accompanied by correspondingly low level of serum alpha tocopherol suggesting potential need for vitamin E supplementation.

Does aerobic exercise induced-analgesia occur through hormone and inflammatory cytokine-mediated mechanisms in primary dysmenorrhea?

The popular accepted explanation for the pathogenesis of primary dysmenorrhea is elevated levels of uterine prostaglandins. Aetiological studies report that production of prostaglandins is controlled by the sex hormone progesterone, with prostaglandins and progesterone displaying an inverse relationship (i.e. increased progesterone levels reduce prostaglandin levels). Pro-inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]) are also implicated in the pathogenesis of primary dysmenorrhea. High-intensity aerobic exercise is effective for decreasing pain quality and intensity in women with primary dysmenorrhea. However, why and how aerobic exercise is effective for treatment of primary dysmenorrhea remain unclear. Our preliminary non-randomized controlled pilot study to examine the effects of high-intensity aerobic exercise on progesterone, prostaglandin metabolite (13,14-dihydro-15-keto-prostaglandin F2 alpha (KDPGF2α), TNF-α, and pain intensity found increases in progesterone and decreases in KDPGF2α, TNF-α, and pain intensity following high-intensity aerobic exercise relative to no exercise. Given these promising preliminary findings, as well as what is known about the pathogenesis of primary dysmenorrhea, we propose the following scientific hypothesis: high-intensity aerobic exercise utilizes hormone (progesterone) and inflammatory cytokine-mediated mechanisms to reduce the pain associated with primary dysmenorrhea.

The impact of circulating 25-hydroxyvitamin and oral cholecalciferol treatment on menstrual pain in dysmenorrheic patients.

This study aims to determine Vitamin-D level in patients with primary dysmenorrhea and investigate the effect of Vitamin-D replacement on symptoms. About 100 patients in the 18-30 age group followed-up with primary dysmenorrhea diagnosis were included in this observational study. The pain severity was assessed using the visual analog scale (VAS). 25-hydroxy vitamin D(25(OH)D) levels of the patients were measured and the replacement therapy was applied according to measurement results. The patients were followed for three months in total. At the end of the three-month period, the 25(OH)D level was measured and the VAS score was assessed once more after the therapy. 25(OH)D level was insufficient in 23.0%, deficient in 45.0%, and severely deficient in 32.0% of the patients. It was found that the VAS score increased as the 25(OH)D level decreased (r = -0.320; p = .002). A significant reduction was observed in VAS scores after Vitamin-D treatment in all three groups; the amount of reduction in VAS score was determined to be higher in the patients with severely deficient levels of 25(OH)D, compared to the patients with deficient or insufficient levels (p < .001). A significant and negative correlation was found between Vitamin-D and symptoms associated with dysmenorrhea in our study. The Vitamin-D replacement therapy led to a significant decrease in symptoms.

Effect of chlorella supplementation on systematic symptoms and serum levels of prostaglandins, inflammatory and oxidative markers in women with primary dysmenorrhea.

OBJECTIVE: Primary dysmenorrhea is one of the most commonly reported disorders for women that have unfavorable effects on patient's quality of life. Based on the evidences that suggest the anti-inflammatory and analgesic properties of chlorella, this double-blind, randomized, placebo controlled clinical trial aimed to evaluate the effects of Chlorella supplementation on the severity of menstrual pain in a group of young women with primary dysmenorrhea. STUDY DESIGN: In this clinical trial, 44 girls with primary dysmenorrhea were randomly divided into intervention and control groups. Patients in the intervention group received 1500 mg/day of chlorella as 5 soft gel and the control group received placebo soft gels for eight weeks. Menstrual and food information were collected using a previously validated and published questionnaire. Anthropometric measurements and biochemical parameters including prostaglandin E2 (PGE2), ProstaglandinF2a (PGF2a), high-sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA) were assessed at baseline and end of week eight. RESULTS: In chlorella supplemented group the PGE2, PGF2a, hs-CRP and MDA decreased significantly (P < 0.05). The severity and duration of dysmenorrheal pain were significantly reduced in the intervention group compared to the control group (p < 0.05). Systemic symptoms of dysmenorrhea (fatigue, headache, nausea, vomiting, lack of energy) decreased in the chlorella group (p < 0.05). The mean of menstrual characteristics, anthropometric indices and daily energy and macronutrient intake in both intervention and control groups were not changed significantly. CONCLUSION: This study showed that chlorella supplementation could decrease the severity of pain and systemic symptoms and improve serum levels of prostaglandins, inflammatory and oxidative markers in women with primary dysmenorrhea.

Serum vitamin D concentrations in young Turkish women with primary dysmenorrhea: A randomized controlled study.

OBJECTIVE: This study aims to investigate the possible role of vitamin D deficiency in primary dysmenorrhea by assessing serum 25-hydroxyvitamin D3 levels in a cohort which includes young Turkish women with primary dysmenorrhea and healthy controls. MATERIALS AND METHODS: A total of 683 women who were aged between 18 and 25 years and who were consecutively admitted to the study center were eligible. After the exclusion of 55 women, 184 women with primary dysmenorrhea were randomly assigned into the dysmenorrhea group and 184 women without dysmenorrhea were randomly allocated into the control group. RESULTS: The dysmenorrhea group had significantly less consumption of dairy products (p = 0.001), lower serum calcium (p = 0.001), lower serum vitamin D (p = 0.001) and higher serum parathyroid hormone (p = 0.001) than those of the control group. Hyperparathyroidism was significantly less frequent whereas vitamin D deficiency was significantly more frequent in the dysmenorrhea group (p = 0.001 for each). The dysmenorrhea patients with vitamin D deficiency had significantly higher visual analogue scale (VAS) scores (p = 0.001). Depression, irritability, mood swings, fatigue, headache and breast tenderness were significantly more frequent in the vitamin D deficiency group (p < 0.05 for all). The VAS scores of the dysmenorrhea patients correlated positively and significantly with serum parathyroid hormone levels (r = 0.666, p = 0.001) whereas these VAS scores correlated negatively and significantly with serum vitamin D levels (r = -0.713, p = 0.001). DISCUSSION: The significant and positive correlation between vitamin D levels and VAS scores and the significant reduction in serum vitamin D levels of the dysmenorrhea patients designate the possible role of vitamin D deficiency in the primary dysmenorrhea.

Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study.

Primary dysmenorrhea (PD), as characterized by painful menstrual cramps without organic causes, is associated with central sensitization and brain function changes. Previous studies showed the integrated role of the default mode network (DMN) in the pain connectome and its key contribution on how an individual perceives and copes with pain disorders. Here, we aimed to investigate whether the cingulum bundle connecting hub regions of the DMN was disrupted in young women with PD. Diffusion tensor imaging was obtained in 41 PD patients and 41 matched healthy controls (HC) during their periovulatory phase. The production of prostaglandins (PGs) was obtained in PD patients during their pain-free and pain phases. As compared with HC, PD patients had similar scores of pain intensity, anxiety, and depression in their pain-free phase. However, altered white matter properties mainly located in the posterior section of the cingulum bundle were observed in PD. Besides PGs being related to menstrual pain, a close relationship was found between the white matter properties of the cingulum bundle during the pain-free phase and the severity of the menstrual pain in PD patients. Our study suggested that PD had trait changes of white matter integrities in the cingulum bundle that persisted beyond the time of menstruation. We inferred that altered anatomical connections may lead to less-flexible communication within the DMN, and/or between the DMN and other pain-related brain networks, which may result in the central susceptibility to develop chronic pain conditions in PD's later life. Hum Brain Mapp 38:4430-4443, 2017. © 2017 Wiley Periodicals, Inc.

Moxibustion for pain relief in patients with primary dysmenorrhea: A randomized controlled trial.

BACKGROUND: Though moxibustion is frequently used to treat primary dysmenorrhea in China, relevant evidence supporting its effectiveness is still scanty. METHODS: This study was a pragmatic randomized, conventional drug controlled, open-labeled clinical trial. After initial screen, 152 eligible participants were averagely randomized to receive two different treatment strategies: Moxibustion and conventional drugs. Participants and practitioners were not blinded in this study. The duration of each treatment was 3 months. The primary outcome was pain relief measured by the Visual Analogue Scale. The menstrual pain severity was recorded in a menstrual pain diary. RESULTS: 152 eligible patients were included but only 133 of them eventually completed the whole treatment course. The results showed that the menstrual pain intensity in experimental group and control group was reduced from 6.38±1.28 and 6.41±1.29, respectively, at baseline, to 2.54±1.41 and 2.47±1.29 after treatment. The pain reduction was not significantly different between these two groups (P = 0.76), however; the pain intensity was significantly reduced relative to baseline for each group (P<0.01). Three months after treatment, the effectiveness of moxibustion sustained and started to be superior to the drug's effect (-0.87, 95%CI -1.32 to -0.42, P<0.01). Secondary outcome analyses showed that moxibustion was as effective as drugs in alleviating menstrual pain-related symptoms. The serum levels of pain mediators, such as PGF2α, OT, vWF, ß-EP, PGE2, were significantly improved after treatment in both groups (P<0.05). No adverse events were reported in this trial. CONCLUSIONS: Both moxibustion and conventional drug showed desirable merits in managing menstrual pain, given their treatment effects and economic costs. This study as a pragmatic trial only demonstrates the effectiveness, not the efficacy, of moxibustion for menstrual pain. It can't rule out the effect of psychological factors during treatment process, because no blind procedure or sham control was used due to availability. In clinical practice, moxibustion should be used at the discretion of patients and their physicians. TRIAL REGISTRATION: ClinialTrials.gov NCT01972906.

The correlation of serum asymmetric dimethylarginine and anti-Müllerian hormone in primary dysmenorrhea.

In this study, we aimed to investigate the association of serum asymmetric dimethylarginine (ADMA) and anti-Müllerian hormone (AMH) levels in primary dysmenorrhea patients. The study employed a cross-sectional design. Eighty-nine female university students with primary dysmenorrhea were included in the study. All patients underwent complete clinical and laboratory investigations, including serum ADMA, AMH levels, pelvic ultrasonography, electrocardiography, and echocardiography. Pearson correlation and linear regression analysis were used to evaluate associations between continuous data. Categorical associations were evaluated using χ(2) test. Correlation analysis between serum ADMA and AMH levels in the study group showed a highly significant positive relationship (Pearson correlation = 0.978, p = 0.01). Our study has shown a significant positive correlation between serum ADMA and AMH levels in primary dysmenorrhea. Serum ADMA levels may have the potential to demonstrate ovarian reserve.

Mean Platelet Volume, a Novel Biomarker in Adolescents with Severe Primary Dysmenorrhea.

STUDY OBJECTIVE: To evaluate whether mean platelet volume (MPV) would be a profitable marker in predicting disease severity in adolescents with severe primary dysmenorrhea (PD). DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A total of 67 patients diagnosed with PD and 37 healthy adolescents with regular menstrual cycles were included in the study. Hemoglobin, MPV, and white blood cell, platelet, lymphocyte, and neutrophil counts were measured as part of the automated complete blood examination. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were obtained from the absolute neutrophil or platelet count, respectively, divided by the absolute lymphocyte count. The visual analog scale was used to assess the level of pain, as mild (<40 mm), moderate (40-60 mm) and severe (>60 mm) PD. RESULTS: The MPV level of the combined severity of PD and control groups were similar. However, the MPV was significantly lower in the severe PD group compared with the control group (P = .04). There were no significant differences in the other hematological parameters between the groups. The mean visual analog scale score of the PD and control subjects were 7.35 ± 2.25 and 1.07 ± 1.96, respectively (P < .01). There was a poor negative correlation, which was statistically insignificant, between MPV and white blood cell count. CONCLUSION: The present study showed that MPV is decreased in adolescents with severe PD. Further studies with larger numbers of subjects are necessary to clarify the roles of platelets in the pathogenesis of severe PD and evaluate the changes in MPV value in response to treatment.

Effect of Bushenwenyanghuayu decoction on nerve growth factor and bradykinin/bradykinin B1 receptor in a endometriosis dysmenorrhea mouse model.

OBJECTIVE: To observe the effects of Bushenwenyanghuayu decoction (BD), a Traditional Chinese Medicine (TCM), on the serum concentration of nerve growth factor (NGF) and bradykinin (BK), and protein and mRNA levels of NGF and bradykinin B1 receptor (BKB1R) in a mouse model of endometriosis dysmenorrhea. METHODS: Seventy-five experimental female BALB/c mice were randomly divided into five groups, 15 mice each: sham, model, BD high dose (61.67 g/kg), BD low dose (15.42 g/kg), and gestrinone (0.4 mg/kg) groups. All the mice except for those in the sham group underwent auto-transplantation surgery and were gavaged estradiol valerate (0.5 mg/kg, daily for 12 days) after surgery. On the 12th day, 1 h after administration, writhing response was induced by intraperitoneal injection of oxytocin at 2 U/mouse. The writhing frequency and latency were recorded and the volume of the ectopic foci was measured. The concentration of serum NGF and BK was detected by enzyme-linked immunosorbent assay, the protein expression of NGF and BKB1R was tested by immunohistochemistry and western blotting, and NGF and BKB1R mRNAs were detected by real-time PCR. RESULTS: Compared with the model group, the volume of the ectopic foci in the treatment groups was significantly lower (P < 0.01), the writhing frequency was decreased (P < 0.05), and the writhing latency was prolonged (P < 0.01). Compared with the sham group, serum NGF and BK levels in the model group were significantly increased (P < 0.01). There were positive correlations for writhing frequency among the NGF and BK groups (P < 0.01). The serum NGF and BK levels were significantly lower in the treatment groups than the model group (P < 0.05). The protein expression of NGF, BKB1R was significantly decreased in the treatment groups compared with the model group (P < 0.01). NGF and BKB1R mRNA expression was significantly decreased in the treatment groups compared with the model group (P < 0.01). CONCLUSION: NGF and BK/BKB1R may play an important role in the development of endometriosis-associated dysmenorrhea, and BD was found to inhibit the development of endometriosis and relieve dysmenorrhea by influencing NGF and BK/ BKB1R mRNA and protein levels.

The role of hypoxia at primary dysmenorrhea, utilizing a novel hypoxia marker--SCUBE1.

STUDY OBJECTIVE: To determine the SCUBE1 levels in adolescents with primary dysmenorrhea. DESIGN: A prospective cross-sectional study. SETTING: A university hospital outpatient clinic, Rize, Turkey. PARTICIPANTS: A total of 40 adolescent girls, 15 on menses and 25 not on menses. INTERVENTIONS AND MAIN OUTCOME MEASURES: Demographic features and menstrual history of the participants were assessed and blood samples were obtained for detecting the platelet volume, platelet counts, and SCUBE1 levels of the participants. RESULTS: No difference was detected between the 2 groups in mean platelet volume, platelet count, and SCUBE1 levels. CONCLUSION: Future trials are required to investigate the relation between SCUBE1 levels and primary dysmenorrhea.

Association of antimüllerian hormone levels with menstrual-cycle type and dysmenorrhea in young asymptomatic women.

OBJECTIVE: To examine the association between antimüllerian hormone (AMH) levels and menstrual-cycle and lifestyle characteristics among young Japanese women. DESIGN: Cross-sectional study. SETTING: University. PATIENT(S): Female students aged 20-22 years (n=65) who had never used oral contraceptives. INTERVENTION(S): Participants completed a questionnaire on reproductive and lifestyle characteristics, and kept a menstrual-cycle diary for 5 consecutive months. Serum AMH was measured once during the study period. MAIN OUTCOME MEASURE(S): Serum AMH concentration. RESULT(S): Compared with women with very mild menstrual pain, serum AMH concentration was 49.6% (95% CI 6.5%-72.8%) lower among women with severe menstrual pain. Higher AMH concentration was associated with irregular menstrual cycles. Even after adjusting for menstrual-cycle regularity and its interaction, more-severe menstrual pain was associated with significantly lower AMH concentration. CONCLUSION(S): Circulating AMH concentration was significantly lower among young Japanese women who had more-severe menstrual pain. Underlying physiological mechanisms need to be addressed in future studies.

Vitamin D and PTH status among adolescent and young females with severe dysmenorrhea.

OBJECTIVE: To investigate Vitamin D and parathyroid hormone (PTH) status among adolescent and young females with severe and very severe dysmenorrhea. DESIGN: Cross-sectional study in specific selected sample. SETTING: One Jordanian university. PARTICIPANTS: Fifty-six females, ages between 17 and 24 years, with severe and very severe dysmenorrhea were surveyed regarding demographics, pain with menstruation, and dietary intake of dairy products. Plasma Vitamin D, PTH levels were measured. RESULTS: About 61% of the studied population experience very severe dysmenorrhea. Half of participants had dairy intake less than 1 serving per day. The majority of participants (80%) had insufficient plasma vitamin D and 48% of them had hyperparathyroidism. CONCLUSION: A high prevalence of vitamin D insufficiency and secondary hyperparathyroidism and/or low dietary calcium intake among adolescent and young adult females who experience severe and very severe dysmenorrhea may negatively affect bone metabolism during achievement of peak bone mass at a young age and adverse bone health at older age.

Plasma metabolic profiling of normal and dysmenorrhea syndrome rats and the effects of Xiang-Fu-Si-Wu Decoction intervention.

CONTEXT: Primary dysmenorrhea (PDM), a common, clinically heterogeneous endocrine disorder affecting young women, is associated with endocrinopathy and metabolic abnormalities. The Xiang-Fu-Si-Wu Decoction (XFSWD) is a traditional Chinese medicine preparation used to treat PDM. OBJECTIVE: In the current study, a plasma metabonomics method based on the ultra-high-performance liquid chromatography-quantitative time-of-flight-mass spectrometry (UHPLC-Q-TOF-MS) system was employed to examine the mechanism of XFSWD action in PDM. MATERIALS AND METHODS: Estradiol benzoate (0.01 g/kg/d) and oxytocin (5 mL/kg) were used to create the dysmenorrhea rat model. Based on the chromatographic data of plasma samples at different time-points following oral administration of XFSWD mixed in water (37.8 g crude herbs/kg) on day 7, partial least square (PLS) and discriminate analysis (DA) were applied to visualize group differentiation and marker selection. RESULTS: Systemic changes occurring in PDM reflect alterations in not only uterus function but also whole-body metabolism. The XFSWD was effective as a therapeutic agent for PDM by reflect metabolic pathway. Prostaglandins and lysophospholipids were identified as two marker types for oxytocin-induced dysmenorrhea syndrome, including LysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0), PGJ2, 11-deoxy-11-methylene-PGD2, 15-deoxy-δ-12,14-PGJ2, LysoPC(20:3), etc. Specifically, the concentrations of prostaglandins compounds (PGJ2, 11-deoxy-11-methylene-PGD2, 15-deoxy-δ-12,14-PGJ2) were increased while those of lysophospholipid compounds [lysoPC(18:4), LysoPE(22:2/0:0), LysoPC(17:0)] were decreased to a significant extent (p < 0.05) in dysmenorrheal rats. Upon treatment with the XFSWD at 12 h, the concentrations of lysophospholipids showed no significant differences (P > 0.05) between the model and normal groups. The lysophospholipid levels were restored. Lysophospholipids were the key factors in phospholipid metabolism. Thus, disruption of phospholipids metabolism appears critical for the development of dysmenorrhea. The XFSWD exerted its effects by interfering with the sphingolipid metabolic pathway. DISCUSSION AND CONCLUSIONS: The metabonomics method presents a promising tool to treat PDM in animal models, and may be applicable for clinical treatment of the human disease in the future.