Can animal models resemble a premenstrual dysphoric condition?

Around 80% of women worldwide suffer mild Premenstrual Disorders (PMD) during their reproductive life. Up to a quarter are affected by moderate to severe symptoms, and between 3% and 8% experience a severe form. It is classified as premenstrual syndrome (PMS) with predominantly physical symptoms and premenstrual dysphoric disorder (PMDD) with psychiatric symptoms. The present review analyzes the factors associated with PMD and the Hypothalamus-Pituitary-Ovarian or Hypothalamus-Pituitary-adrenal axis and discusses the main animal models used to study PMDD. Evidence shows that the ovarian hormones participate in PMDD symptoms, and several points of regulation of their synthesis, metabolism, and target sites could be altered. PMDD is complex and implies several factors that require consideration when this condition is modeled in animals. Of particular interest are those points related to areas that may represent opportunities to develop new approximations to understand the mechanisms involved in PMDD and possible treatments.

Key to Life: Physiological Role and Clinical Implications of Progesterone.

The most recent studies of progesterone research provide remarkable insights into the physiological role and clinical importance of this hormone. Although the name progesterone itself means "promoting gestation", this steroid hormone is far more than a gestational agent. Progesterone is recognized as a key physiological component of not only the menstrual cycle and pregnancy but also as an essential steroidogenic precursor of other gonadal and non-gonadal hormones such as aldosterone, cortisol, estradiol, and testosterone. Based on current findings, progesterone and novel progesterone-based drugs have many important functions, including contraception, treatment of dysfunctional uterine bleeding, immune response, and prevention of cancer. Considering the above, reproduction and life are not possible without progesterone; thus, a better understanding of this essential molecule could enable safe and effective use of this hormone in many clinical conditions.

Food cue-elicited brain potentials change throughout menstrual cycle: Modulation by eating styles, negative affect, and premenstrual complaints.

BACKGROUND: While there is evidence for increased food intake and craving during the luteal phase, underlying mechanisms are incompletely understood. The present study investigated electrophysiological responses to food pictures as a function of menstrual cycle phase. In addition, the moderating effects of progesterone, eating behaviors (restraint, emotional, orthorexic), negative affect, and premenstrual complaints were explored. METHODS: Using a within-subject design, 35 free-cycling women watched and rated pictures of food (high and low caloric) and control items during the follicular, the ovulatory, and the luteal phase (counterbalanced), while EEG was recorded to examine the late positive potentials (LPP). Salivary gonadal hormones and affect were examined at each occasion. Eating behaviors and premenstrual complaints were assessed once. RESULTS: For parietal regions, average LPPs were comparable between cycle phases but slightly larger LPP amplitudes were elicited by high caloric food pictures as compared to the neutral category. Descriptively, both food categories elicited larger parietal LPPs than neutral pictures during the luteal phase. Analyses of LPPs for central-parietal regions showed no effect of picture category or cycle phase, except higher amplitudes in the right area during the luteal phase. During the luteal phase, progesterone and functional interference from premenstrual symptoms (but not age, BMI, picture ratings, affect, estradiol, or eating behaviors) significantly predicted larger parietal LPPs towards high caloric (but not low caloric) pictures. CONCLUSION: Our findings suggest a heightened food cue reactivity during the luteal phase, which may relate to higher ovarian hormone secretion and more functional impact of premenstrual symptoms. This research contributes to a better understanding of menstrual health and the identification of preventive strategies for premenopausal women.

Premenstrual syndrome is associated with altered cortisol awakening response.

Previous studies have revealed stress-induced dysregulation of hypothalamic-pituitary-adrenal (HPA) axis in women with premenstrual syndrome (PMS). So far, however, the results about the relationship between HPA axis dysregulation and PMS are mixed. To this end, it is necessary to investigate the basal activity of the HPA axis in women with PMS instead of only assessing a certain stressor. Therefore, this study evaluated the relationship between the cortisol awakening response (CAR) and PMS. Thirty-two women with PMS (mean age 22.47 ± 2.20 years) and 36 healthy controls (mean age 22.28 ± 2.43 years) were included in this study. Saliva samples of our participants were collected successively at 0, 30, 45, and 60 min after awakening to assess CAR during each of two phases of the menstrual cycle (the mid-follicular phase and the late luteal phase). The results showed a significantly attenuated CAR in women with PMS compared with the healthy controls, especially at 45 and 60 min after awakening, regardless of the menstrual cycle phases. Furthermore, there was a significant negative correlation between PMS severity as measured by PMS scale and AUCi (i.e. the Area Under the Curve with respect to increase) in the mid-follicular phase. Our findings suggested that an attenuated CAR activity profile may be an important risk factor for the development of PMS.

Perimenstrual exacerbation of symptoms in borderline personality disorder: evidence from multilevel models and the Carolina Premenstrual Assessment Scoring System.

BACKGROUND: Individuals with a borderline personality disorder (BPD) suffer from a constellation of rapidly shifting emotional, interpersonal, and behavioral symptoms. The menstrual cycle may contribute to symptom instability among females with this disorder. METHODS: Fifteen healthy, unmedicated females with BPD and without dysmenorrhea reported daily symptoms across 35 days. Urine luteinizing hormone and salivary progesterone (P4) were used to confirm ovulation and cycle phase. Cyclical worsening of symptoms was evaluated using (1) phase contrasts in multilevel models and (2) the Carolina Premenstrual Assessment Scoring System (C-PASS), a protocol for evaluating clinically significant cycle effects on symptoms. RESULTS: Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD). CONCLUSIONS: Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD.

Low Proportion of Dietary Plant Protein among Athletes with Premenstrual Syndrome-Related Performance Impairment.

Premenstrual syndrome (PMS) is psychosomatic disorder that are limited to the late luteal phase in the menstrual cycle. PMS could impair athletic performance. To investigate associations between proportions of dietary plant and animal protein and PMS-related impairment of athletic performance, we surveyed 135 female athletes aged 18-23 years attending Kindai University. Participants belonged to authorized university clubs, all of which have high rankings in Japanese university sports. Participants completed self-administered questionnaires on diet history, demographics, and PMS-related impairment of athletic performance. Total protein, animal protein, and plant protein intake were examined, and the proportion of dietary plant protein was calculated for each participant. We divided athletes into two groups: those without PMS-related impairment of athletic performance (n = 117) and those with PMS-related performance impairment (n = 18). A t-test was used to compare mean values and multivariable adjusted mean values between groups; adjustment variables were energy intake, body mass index, and daily training duration. Total protein intake was not significantly different between the groups. However, athletes whose performance was affected by PMS reported higher intake of animal protein (mean 50.6 g) than athletes whose performance was unaffected by PMS (mean 34.9 g). Plant protein intake was lower among athletes with PMS-related impairment (mean 25.4 g) than among athletes without impairment (mean 26.9 g). The proportion of dietary plant protein was lower among athletes with PMS-related impairment (39.3%) than those without impairment (45.9%). A low proportion of dietary plant protein may cause PMS-related athletic impairment among athletes.

Profiling Proteins in the Hypothalamus and Hippocampus of a Rat Model of Premenstrual Syndrome Irritability.

Premenstrual syndrome (PMS) refers to several physical and mental symptoms (such as irritability) commonly encountered in clinical gynaecology. The incidence of PMS has been increasing, attracting greater attention from medical fields. However, PMS pathogenesis remains unclear. This study employed two-dimensional gel electrophoresis (2DE) for proteomic map analysis of the hypothalamus and hippocampus of rat models of premenstrual syndrome (PMS) irritability. Matrix-assisted laser desorption/ionisation time of flight mass spectroscopy (MALDI-TOF-MS) was used to identify proteins possibly related with PMS irritability. Baixiangdan, a traditional Chinese medicine effective against PMS irritability, was used in the rat model to study putative target proteins of this medicine. The hypothalamus and hippocampus of each group modelling PMS displayed the following features: decreased expression of Ulip2, tubulin beta chain 15, α actin, and interleukin 1 receptor accessory protein; increased expression of kappa-B motif-binding phosphoprotein; decreased expression of hydrolase at the end of ubiquitin carboxy, albumin, and aldolase protein; and increased expression of M2 pyruvate kinase, panthenol-cytochrome C reductase core protein I, and calcium-binding protein. Contrasting with previous studies, the current study identified new proteins related to PMS irritability. Our findings contribute to understanding the pathogenesis of PMS irritability and could provide a reference point for further studies.

Shuyu Capsules Relieve Premenstrual Syndrome Depression by Reducing 5-HT3AR and 5-HT3BR Expression in the Rat Brain.

The effects of the Shuyu capsule on 5-HT3AR and 5-HT3BR expression in a rat model of premenstrual syndrome (PMS) depression and on 5-HT3AR and 5-HT3BR expression and hippocampal neuron 5-HT3 channel current were investigated, to elucidate its mechanism of action against PMS depression. PMS depression model rats were divided into depression and Shuyu- and fluoxetine-treated groups, which were compared to control rats for frontal lobe and hippocampal 5-HT3AR and 5-HT3BR expression and behavior. The depressed model rats displayed symptoms of depression, which were reduced in treated and normal control rats. Frontal lobe and hippocampal 5-HT3AR and 5-HT3BR levels were significantly higher in the model versus the control group and were significantly lower in the Shuyu group. As compared to control rats, the 5-HT3R channel current in the model group was significantly higher; the 5-HT3R channel current in hippocampal neurons treated with serum from Shuyu group rats was significantly lower than that in those treated with model group serum. Thus, PMS depression may be related to 5-HT3AR and 5-HT3BR expression and increased 5-HT3 channel current. Shuyu capsules rectified abnormal 5-HT3AR and 5-HT3BR expression and 5-HT3 channel current changes in a rat model; this finding may provide insight into treating PMS depression.

Premenstrual syndrome is associated with blunted cortisol reactivity to the TSST.

This study assessed the effects of premenstrual syndrome (PMS) and menstrual phases on the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system axis and psychological responses to the Trier Social Stress Test (TSST). Thirty-six PMS women (mean age 21.69 ± 2.16 years) and 36 control women (mean age 22.03 ± 2.48 years) participated in the TSST task, either in the follicular phase or in the late luteal phase (each group N = 18). Saliva samples, heart rate and subjective stress levels were collected for seven time points throughout the test (10, 20, 30, 40, 55, 70 and 100 min). The results indicated that in comparison with control women, PMS women displayed blunted cortisol stress responses to the TSST irrespective of the menstrual phases, as indexed by the cortisol levels across time, area under the curve with respect to ground (AUCg) and peak change scores of cortisol. The results also demonstrated that the measurements indexed by cortisol levels across time, AUCg and peak change scores of heart rate were smaller in women tested during the late luteal phase than during the follicular phase. Correlation results indicated that AUCg was negatively correlated with PMS scores. These results suggest that measures of cortisol, rather than heart rate or subjective responses to stress, may be most closely associated with PMS. Furthermore, hypo-reactivity of the HPA axis may be pathologically relevant to PMS because it predicts heightened PMS severity.

Association of inflammation markers with menstrual symptom severity and premenstrual syndrome in young women.

STUDY QUESTION: Are markers of chronic inflammation associated with menstrual symptom severity and premenstrual syndrome (PMS)? SUMMARY ANSWER: Serum levels of inflammatory markers, including interleukin (IL)-2, IL-4, IL-10, IL-12 and interferon (IFN)-γ were positively associated with menstrual symptom severity and/or PMS in young women. WHAT IS KNOWN ALREADY: Chronic inflammation has been implicated in the etiology of depression and other disorders that share common features with PMS, but whether inflammation contributes to menstrual symptom severity and PMS is unknown. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 277 women aged 18-30 years, conducted in 2006-2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants provided information on menstrual symptoms, lifestyle, diet, anthropometry and other factors by questionnaire and/or direct measurement, and a mid-luteal phase fasting blood sample was taken between 7 a.m. and 12 p.m. Total, physical and affective menstrual symptom scores were calculated for all participants, of whom 13% (n = 37) met criteria for moderate-to-severe PMS and 24% (n = 67) met PMS control criteria. Inflammatory factors assayed in serum included IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α, granulocyte macrophage colony stimulating factor, IFN-γ and C-reactive protein. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for age, smoking status and BMI, total menstrual symptom score was positively associated with levels of IL-2 (percentage difference in women at the 75th percentile of total symptom score versus at the 25th percentile = 24.7%; P = 0.04), IL-4 (21.5%; P = 0.04), IL-10 (28.0%; P < 0.01) and IL-12 (42.0%; P = 0.02) in analyses including all participants. Affective menstrual symptom score was linearly related to levels of IL-2 (percentage difference at 75th percentile versus 25th percentile = 31.0%; P = 0.02), while physical/behavioral symptom score was linearly related to levels of IL-4 (19.1%; P = 0.03) and IL-12 (33.2%; P = 0.03). Additionally, mean levels of several factors were significantly higher in women meeting PMS criteria compared with women meeting control criteria, including IL-4 (92% higher in cases versus controls; P = 0.01); IL-10 (87%; P = 0.03); IL-12 (170%; P = 0.04) and IFN-γ (158%; P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Our study has several limitations. While a single blood sample may not perfectly capture long-term levels of inflammation, ample data suggest that levels of cytokines are stable over time. Although we did not base our assessment of PMS on prospective symptom diaries, we used validated criteria to define PMS cases and controls, and excluded women with evidence of comorbid mood disorders. Furthermore, because of the cross-sectional design of the study, the temporal relation of inflammatory factors and menstrual symptoms is unclear. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is among the first studies to suggest that inflammatory factors may be elevated in women experiencing menstrual symptoms and PMS. Additional studies are needed to determine whether inflammation plays an etiologic role in PMS. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Departments of Public Health and Nutrition and by a Faculty Research Grant, University of Massachusetts Amherst. No conflicts declared. TRIAL REGISTRATION NUMBER: N/A.

Sexuality and androgens in women with cyclical mood changes and pre-menstrual syndrome.

OBJECTIVE: To study the relation between androgen levels and sexual interest in women with different kinds of pre-menstrual syndrome (PMS). DESIGN: Causal comparative study. SETTING: Swedish university hospital outpatient clinic. POPULATION: Seventy women with cyclical mood changes. METHODS: Pre-menstrual syndrome patients were divided into those with and those without preovulatory symptoms. In 37 women, early follicular phase blood samples were analyzed for androstenedione, testosterone, sex hormone-binding globulin (SHBG), progesterone and estradiol, using radioimmunoassay. The participants were divided into subgroups depending on whether the levels of androgens and SHBG were above or below the median. In 33 of them it was possible to compare the cyclicity in sexual parameters between these subgroups. MAIN OUTCOME MEASURES: Daily ratings of sexual parameters and hormonal analyses. RESULTS: Plasma testosterone was significantly lower and SHBG significantly higher in women with luteal phase symptoms compared with those with additional follicular phase symptoms. ANOVA showed significant cyclicity for all sexual parameters consistently. For the "sexual feelings" and "pleasant sexual thoughts" parameters, cyclicity was the same whether or not the hormonal levels were "high" or "low." CONCLUSIONS: The "Pure-PMS" group and the "pre-menstrual-exacerbation" groups differed in their androgen and SHBG levels. Women suffering from PMS with higher neuroticism Eysenck Personality Inventory scores or "low" levels of androgens and SHBG would be more likely to have a decreased sexual interest pre-menstrually than would women with a high level.

Depressive mood and frontal alpha asymmetry during the luteal phase in premenstrual dysphoric disorder.

AIMS: Patients with premenstrual dysphoric disorder (PMDD) experience moderate to severe physical and mood symptoms during the luteal phase of their menstrual cycle. The purposes of this study were to examine whether there were significant differences in frontal alpha asymmetry between PMDD and non-PMDD women during a depressive induction condition during the luteal and follicular phases and to examine the relations between premenstrual distress and depressive symptoms, and frontal alpha asymmetry. MATERIAL AND METHODS: The participants included 12 college women with PMDD and 12 without PMDD as controls. Frontal electroencephalograms (F3/F4) were measured during the luteal and follicular phases of the menstrual cycle in the following sequence: resting baseline, depressive induction, depressive recall, recovery, and relaxation. Premenstrual distress questionnaires and the Beck Depression Inventory II were administered. RESULTS: The participants with PMDD had higher frontal alpha asymmetry than those without PMDD during the depressive induction and relaxation conditions only during the luteal phase. For PMDD and non-PMDD during the luteal phase, a positive correlation was observed between negative affect (measured by premenstrual distress questionnaires) and frontal alpha asymmetry under the depressive induction stage. In addition, higher Beck Depression Inventory II somatic depression was positively correlated with frontal alpha asymmetry under the depressive induction stage. CONCLUSIONS: This study supports the significant difference between PMDD and non-PMDD on frontal alpha asymmetry, and frontal alpha asymmetry was related to negative affect and somatic depression, while participants with PMDD were in the depressive mood during the luteal phase.

Effect of curcumin on inflammatory biomarkers and iron profile in patients with premenstrual syndrome and dysmenorrhea: A randomized controlled trial.

Premenstrual syndrome (PMS) and primary dysmenorrhea are common gynecological problems and inflammation may have a role in their etiology. Curcumin is a polyphenolic natural product for which there is increasing evidence of anti-inflammatory and iron chelation effects. This study assessed the effects of curcumin on inflammatory biomarkers and iron profile in young women with PMS and dysmenorrhea. A sample of 76 patients was included in this triple-blind, placebo-controlled clinical trial. Participants were randomly allocated to curcumin (n = 38) and control groups (n = 38). Each participant received one capsule (500 mg of curcuminoid+ piperine, or placebo) daily, from 7 days before until 3 days after menstruation for three consecutive menstrual cycles. Serum iron, ferritin, total iron-binding capacity (TIBC) and high-sensitivity C-reactive protein (hsCRP), as well as white blood cell, lymphocyte, neutrophil, platelet counts, mean platelet volume (MPV) and red blood cell distribution width (RDW), were quantified. Neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) were also calculated. Curcumin significantly decreased the median (interquartile range) serum levels of hsCRP [from 0.30 mg/L (0.0-1.10) to 0.20 mg/L (0.0-1.3); p = 0.041] compared with placebo, but did not show any difference for neutrophil, RDW, MPV, NLR, PLR and RPR values (p > 0.05). The treatment schedule was well-tolerated, and none of markers of iron metabolism statistically changed after the intervention in the curcumin group (p > 0.05). Curcumin supplementation may have positive effects on serum hsCRP, a marker of inflammation, with no any changes on iron homeostasis in healthy women with PMS and dysmenorrhea.

[Effects of jingqianping granule on mRNA and protein expression of mu opioid receptor in premenstrual syndrome gan-qi invasion rats].

OBJECTIVE: To observe the effects of Jingqianping Granule (JG) on mRNA and protein expressions of mu opioid receptor in the parietal cortex and the frontal cortex, the hypothalamus and hippocampus of premenstrual syndrome (PMS) Gan-qi invasion rats. METHODS: Twenty rats were selected to prepare the PMS Gan-qi invasion model. After modeling rats were divided into the model group and the Chinese herb treated group, ten in each group. Another 10 rats were selected as the normal control group. During the modeling, JG (1.6 g/kg) was given to rats in the Chinese herb treated group by gastrogavage, while equal volume of normal saline (1 mL/100 g) was given to rats in normal control group and the model group. All treatment was performed once daily for five successive days. The mRNA and protein expressions of mu opioid receptor in the parietal cortex and the frontal cortex, the hypothalamus and hippocampus were detected using RT-PCR and Western blot respectively. RESULTS: Compared with the normal control group, the bands of products of MOR mRNA and protein in the parietal cortex and the frontal cortex were relatively weaker in the model group, and the optical density value decreased. The MOR mRNA and protein expressions in the parietal cortex and the frontal cortex relatively decreased. But the bands of products of MOR mRNA and protein in the hypothalamus and hippocampus were relatively stronger and optic value increased. The MOR mRNA and protein expressions in the hypothalamus and hippocampus relatively increased with statistical difference (P<0.01, P<0.05). Compared with the model group, the bands of products of MOR mRNA and protein in the parietal cortex and the frontal cortex were relatively enhanced, the MOR mRNA expression in the parietal cortex increased, the MOR protein expression in the parietal cortex and the frontal cortex increased in the Chinese herb treated group. The bands of products of MOR mRNA and protein in the hypothalamus and hippocampus were relatively weaker. The MOR mRNA and protein expressions in the hypothalamus and hippocampus relatively decreased. The MOR protein expression in the hippocampus decreased relatively with statistical difference (P<0.01, P<0.05). CONCLUSIONS: Expression of mu opioid receptor in brains of PMS Gan-qi invasion rats was regionally specific. Administration of JG showed corresponding regulatory effects.

The relationship between bipolar disorder, seasonality, and premenstrual symptoms.

Cyclical mood disorders characterized by shifting affective states include bipolar disorder, seasonal affective disorder, and premenstrual syndrome/premenstrual dysphoric disorder. In this article, we explore the relationship between these disorders and bring the reader up to date on the advances made in the past year in understanding the relationship between bipolar disorder, seasonality, and premenstrual symptoms.

Female reproductive steroids and neuronal excitability.

Oestrogen and progesterone have specific receptors in the central nervous system and are able to regulate neuronal development and plasticity, neuronal excitability, mitochondrial energy production, and neurotransmitter synthesis, release, and transport. On neuronal excitability, estradiol and progesterone seem to have an opposite effect, with estradiol being excitatory and progesterone and its derivative allopregnanolone being inhibitory. Estradiol augments N-methyl-D-aspartate-mediated glutamate receptor activity, while progesterone enhances gamma-aminobutyric acid-mediated chloride conductance. Sex steroid regulation of the balance of neuroexcitatory and neuroinhibitory activities may have a role in modulating clinical susceptibility to different neurological conditions such as migraine, catamenial epilepsy, premenstrual dysphoric disorder, and premenstrual syndrome.

[Study on estrogen receptors alpha and beta in the hippocampus of premenstrual syndrome model rats of gan-qi depression syndrome].

OBJECTIVE: To study the distribution pattern, the protein expressions, and changes of functional activities of estrogen receptor (ER) alpha and beta in the hippocampus of premenstrual syndrome (PMS) rats of Gan-qi depression syndrome (GDS), and to find out corresponding effect targets of Jingqianshu Granule (JG), thus providing clues for exploring the pathogenesis of PMS of GDS and the mechanisms of JG. METHODS: SD rats were randomly divided into three groups, i. e., the normal group, the model group, and the medication group, 7 in each. Resident intruder stress was used to establish the model in the model group and the medication group. JG was given to rats in the medication group at the dose of 10 mL/kg by gastrogavage while modeling. Equal volume of sterilized water was given to rats in the model group and the normal group, once daily, for 5 successive days. Then the location, protein levels, and ligand-binding capacities of ERalpha and ERbeta in the hippocampus of rats in three groups were detected using immunohistochemical assay, Western blot, and dextran-active carbon binding assay. RESULTS: There was no difference in the distribution pattern of ERalpha and ERbeta in the hippocampus of the three groups. In aspects of protein levels and estrogen-binding capacities of ERalpha and ERbeta in the hippocampus, CA1 and CA3 regions, they increased more obviously in the model group than in the normal group (P < 0.05), while they decreased more significantly in the medication group than in the model group (P < 0.05). CONCLUSION: Higher estrogen levels and enhanced expressions and activities of ERalpha and ERbeta in the hippocampus might be important mechanisms for PMS of GDS, which might also be the effect targets for JG.

[Effects of jingqianshu granule on expression of 5-HT(1A)R of PMS model rats with liver-qi stagnation].

OBJECTIVE: To research the effect of the Jingqianshu granule (JQS) on the expression of serotonin receptor-1A (5-HT(1A)R) in hippocampus and hypothalamus of premenstrual syndrome (PMS) model rats with Liver-qi depression. METHOD: The PMS model rats with Liver-qi depression were induced by bandaging the limbs. The model rats were treated with JQS, and evaluated by open-field test. The expression of 5-HT(1A)R in hippocampus and hypothalamus was analysed by the method of RT-PCR and Western blot. RESULT: After the JQS were administered, the open field scores, the expression of 5-HT(1A)R mRNA and protein in hippocampus and hypothalamus of rats increased significantly. CONCLUSION: The JQS granule can up-regulate the expression of 5-HT(1A)R in hippocampus and hypothalamus, which maybe one of the mechanism to treat PMS with liver-qi depression.

Changes in salivary prostaglandin levels during menstrual migraine with associated dysmenorrhea.

OBJECTIVE: To measure prostaglandin levels in the saliva of individuals during menstrual migraine associated with dysmenorrhea (MMaD) and in response to treatment with a single tablet combination of sumatriptan succinate and naproxen sodium. BACKGROUND: Prostaglandins are thought to play a role in MMaD as elevated serum prostaglandin levels have been reported during attacks of menstrual migraine and are increased in the menstrual fluid of women with dysmenorrhea. While triptans are the primary line of migraine treatment, nonsteriodal anti-inflammatory drugs are the most commonly prescribed therapy for dysmenorrhea symptoms. Data from recent clinical studies have provided evidence that treatment with a single tablet combination of sumatriptan and naproxen sodium is an effective abortive therapy for attacks of MMaD. METHODS: Women diagnosed with MMaD were treated with a sumatriptan succinate and naproxen sodium single tablet combination or placebo at time of migraine attack. Saliva samples were collected at time of attack as well as 2 and 4 hours after treatment. PGD(2), PGE(2), PGF(2), PGI(2), and TXA(2) levels were determined by enzyme-linked immunosorbent assay. RESULTS: Elevated levels of PGD(2), PGF(2), and TXA(2) at 2 and 4 hours and PGE(2) at 4 hours were found in saliva obtained from placebo subjects when compared with onset of attack levels. However, in subjects treated with a single tablet combination of sumatriptan and naproxen sodium, the levels of PGD(2), PGF(2), and PGE(2) were not elevated at either time point while TXA(2) levels were still elevated at 4 hours. CONCLUSIONS: Data from this pilot study provide evidence that saliva levels of several prostaglandins increase during attacks of MMaD and that treatment with a single tablet combination of sumatriptan and naproxen sodium prevents elevation of prostaglandin levels.

[Effects of Baixiangdan capsule on location and expression levels of GABA(A) receptor beta2 subunit in hippocampus of PMS model rats with liver-qi invasion].

OBJECTIVE: To explore the effects of Baixiangdan capsule(BXD), a Chinese herbal compound, on the location and expression levels of GABA(A) receptor beta2 subunit (GABA(A)Rbeta2) in hippocampus of PMS model rats with liver-qi invasion. METHOD: After vaginal smear examination and open field test, the selected SD rats were randomly divided into 3 groups Normal group, PMS model group with liver-qi invasion and PMS BXD-administration group with liver-qi invasion (BXD was administered with oral dosage of 10 g x kg(-1) body weight every day for 5 days). PMS model rats with liver-qi invasion were induced by electric stimulating, and evaluated by macro-behavior observation and open-field test. The location and expression of GABA(A) receptor in hippocampus were measured by fluorescence microscopy and western blot respectively. RESULT: Compared with the normal group, the open field scores and GABA(A) Rbeta2 expression of PMS model rats with liver-qi invasion were increased significantly, and the distribution of GABA(A) receptor is more concentrated. However, the scores and GABA(A) beta2 expression of PMS BXD-administration group with liver-qi invasion were decreased markedly. Compared with the PMS model group the location had no significant change. CONCLUSION: One of micro-mechanisms of PMS model rats with liver-qi invasion may be related with the high expression of GABA(A) Receptor beta2 subunit in hippocampus, and the Chinese medicinal formula, BXD granule, had an adjust on the above abnormal changes.