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.

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.

Thalamocortical dysconnectivity in premenstrual syndrome.

Premenstrual syndrome (PMS) is a menstrual cycle-related disorder. Although the precise pathophysiology is not fully understood, it is increasingly believed that the central nervous system plays a vital role in the development of PMS. The aim of this study is to elucidate specific functional connectivity between the thalamus and cerebral cortex. Resting-state functional magnetic resonance imaging (fMRI) data were obtained from 20 PMS patients and 21 healthy controls (HCs). Seed-based functional connectivity between the thalamus and six cortical regions of interest, including the prefrontal cortex (PFC), posterior parietal cortex, somatosensory cortex, motor cortex/supplementary motor area, temporal and occipital lobe, was adopted to identify specific thalamocortical connectivity in the two groups. Correlation analysis was then used to examine relationships between the neuroimaging findings and clinical symptoms. Activity in distinct cortical regions correlated with specific sub-regions of the thalamus in the two groups. Comparison between groups exhibited decreased prefrontal-thalamic connectivity and increased posterior parietal-thalamic connectivity in the PMS patients. Within the PMS group, the daily record of severity of problems (DRSP) score negatively correlated with the prefrontal-thalamic connectivity. Our findings may provide preliminary evidence for abnormal thalamocortical connectivity in PMS patients and may contribute to a better understanding of the pathophysiology of PMS.

Effectiveness of natural S-equol supplement for premenstrual symptoms: protocol of a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Premenstrual syndrome (PMS) comprises a range of mood, behavioural and physical symptoms, and impairs many women's quality of life. Isoflavones are expected to stabilise the natural fluctuation of the oestrogen cycle through their selective oestrogen receptor modulator-like activities that alleviate PMS symptoms. Equol, a metabolite of a soy isoflavone converted from daidzein by specific gut bacteria, has a greater bioavailability compared with other soy isoflavones. We aim to examine the effect of natural S-equol supplements on premenstrual symptoms. METHODS AND ANALYSIS: This study will enrol 124 women (aged 20-45 years) who have PMS symptoms and are non-equol producers in a double-blind, parallel, randomised, placebo-controlled trial, in which they will receive natural S-equol supplement (equol 10 mg a day) or placebo, orally, twice daily, for three menstrual cycles. The primary outcome measure (Daily Record of Severity of Problems total score) will be assessed during intervention cycles. To compare the primary outcomes between the S-equol group and the placebo group, the mean differences in the Daily Record of Severity of Problems total score between the two groups will be determined. The p values will be determined using Student's t-test, where the significance level is 5% (two-sided). ETHICS AND DISSEMINATION: The institutional review board at Kindai University approved the study. The findings of this trial will be submitted to an international peer-reviewed journal. Abstracts will be submitted to national and international conferences. TRIAL REGISTRATION NUMBER: UMIN000031815.

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.

Magnesium in the gynecological practice: a literature review.

A growing amount of evidence suggests that magnesium deficiency may play an important role in several clinical conditions concerning women health such as premenstrual syndrome, dysmenorrhea, and postmenopausal symptoms. A number of studies highlighted a positive correlation between magnesium administration and relief or prevention of these symptoms, thus suggesting that magnesium supplementation may represent a viable treatment for these conditions. Despite this amount of evidence describing the efficacy of magnesium, few and un-systematize data are available about the pharmacological mechanism of this ion for these conditions. Herein, we review and systematize the available evidence about the use of oral magnesium supplementation in several gynecological conditions and discuss the pharmacological mechanisms that characterize these interventions. The picture that emerges indicates that magnesium supplementation is effective in the prevention of dysmenorrhea, premenstrual syndrome, and menstrual migraine and in the prevention of climacteric symptoms.

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.

IgA/IgM responses to tryptophan and tryptophan catabolites (TRYCATs) are differently associated with prenatal depression, physio-somatic symptoms at the end of term and premenstrual syndrome.

There is some evidence that lowered tryptophan and an activated tryptophan catabolite (TRYCAT) pathway play a role in depression, somatoform disorder, and postpartum blues. The aim of this study is to delineate the associations between the TRYCAT pathway and premenstrual syndrome (PMS) and perinatal depressive and physio-somatic symptoms. We examine the associations between end of term serum IgM and IgA responses to tryptophan and 9 TRYCATs in relation to zinc, C-reactive protein (CRP), and haptoglobin and prenatal physio-somatic (previously known as psychosomatic) symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation) and prenatal and postnatal depression and anxiety symptoms as measured using the Edinburgh Postnatal Depression Scale (EPDS), Hamilton Depression Rating Scale (HAMD), and Spielberger's State Anxiety Inventory (STAI). We included pregnant females with (n = 24) and without depression (n = 25) and 24 non-pregnant females. There were no significant associations between the IgA/IgM responses to tryptophan and TRYCATs and prenatal and postnatal depression/anxiety symptoms, except for lowered IgA responses to anthranilic acid in prenatal depression. A large part of the variance in IgA responses to most TRYCATs was explained by PMS and haptoglobin (positively) and CRP (inversely) levels. The IgA responses to TRYCATs were significantly increased in PMS, in particular picolinic, anthranilic, xanthurenic and kynurenic acid, and 3OH-kynurenine. Variance (62.5%) in physio-somatic symptoms at the end of term was explained by PMS, previous depressions, zinc (inversely), CRP and haptoglobin (both positively), and the IgM responses to quinolinic acid (positively), anthranilic acid, and tryptophan (both negatively). The results suggest that mucosa-derived TRYCAT pathway activation is significantly associated with PMS, but not with perinatal depression/anxiety symptoms. Physio-somatic symptoms in pregnancy have an immune-inflammatory pathophysiology. Induction of the TRYCAT pathway appears to be more related to physio-somatic than to depression symptoms.

A specific profile of luteal phase progesterone is associated with the development of premenstrual symptoms.

There is a consensus that the development of premenstrual dysphoric states is related to cyclical change in gonadal hormone secretion during the menstrual cycle. However, results from studies seeking to link symptom severity to luteal phase progesterone concentration have been equivocal. In the present study we evaluated not only the absolute concentrations of progesterone but also the kinetics of the change in progesterone concentration in relation to development of premenstrual symptoms during the last 10days of the luteal phase in a population of 46 healthy young adult Brazilian women aged 18-39 years, mean 26.5±6.7years. In participants who developed symptoms of premenstrual distress, daily saliva progesterone concentration remained stable during most of the mid-late luteal phase, before declining sharply during the last 3days prior to onset of menstruation. In contrast, progesterone concentration in asymptomatic women underwent a gradual decline over the last 8days prior to menstruation. Neither maximum nor minimum concentrations of progesterone in the two groups were related to the appearance or severity of premenstrual symptoms. We propose that individual differences in the kinetics of progesterone secretion and/or metabolism may confer differential susceptibility to the development of premenstrual syndrome.

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.

Reproductive Steroid Regulation of Mood and Behavior.

In this article, we examine evidence supporting the role of reproductive steroids in the regulation of mood and behavior in women and the nature of that role. In the first half of the article, we review evidence for the following: (i) the reproductive system is designed to regulate behavior; (ii) from the subcellular to cellular to circuit to behavior, reproductive steroids are powerful neuroregulators; (iii) affective disorders are disorders of behavioral state; and (iv) reproductive steroids affect virtually every system implicated in the pathophysiology of depression. In the second half of the article, we discuss the diagnosis of the three reproductive endocrine-related mood disorders (premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression) and present evidence supporting the relevance of reproductive steroids to these conditions. Existing evidence suggests that changes in reproductive steroid levels during specific reproductive states (i.e., the premenstrual phase of the menstrual cycle, pregnancy, parturition, and the menopause transition) trigger affective dysregulation in susceptible women, thus suggesting the etiopathogenic relevance of these hormonal changes in reproductive mood disorders. Understanding the source of individual susceptibility is critical to both preventing the onset of illness and developing novel, individualized treatments for reproductive-related affective dysregulation. © 2016 American Physiological Society. Compr Physiol 6:1135-1160, 2016e.

A lack of consistent evidence for cortisol dysregulation in premenstrual syndrome/premenstrual dysphoric disorder.

Although decades of research has examined the association between cortisol regulation and premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD), no review exists to provide a general set of conclusions from the extant research. In the present review we summarize and interpret research that has tested for associations between PMS/PMDD and cortisol levels and reactivity (n=38 original research articles). Three types of studies are examined: correlational studies, environmental-challenge studies, and pharmacological-challenge studies. Overall, there was very little evidence that women with and without PMS/PMDD demonstrate systematic and predictable mean-level differences in cortisol, or differences in cortisol response/reactivity to challenges. Methodological differences in sample size, the types of symptoms used for diagnosis (physical and psychological vs. only affective), or the type of cortisol measure used (serum vs. salivary), did not account for differences between studies that did and did not find significant effects. Caution is recommended before accepting the conclusion of null effects, and recommendations are made that more rigorous research be conducted, considering symptom-specificity, within-person analyses, and multiple parameters of cortisol regulation, before final conclusions are drawn.

Integrated theory to unify status among schizophrenia and manic depressive illness.

Tryptophan hydroxylase 1 is primarily expressed in the gastrointestinal tract, and has been associated with both schizophrenia and depression. Although decreased serotonin activity has been reported in both depression and mania, it is important to investigate the interaction between serotonin and other neurotransmitter systems. There are competitive relationships between branched-chain amino acids, and tryptophan and tyrosine that relate to physical activity, and between L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP), both highly dependent on intracellular tetrahydrobiopterin concentrations. Here, I propose a chaos theory for schizophrenia, mania, and depression using the competitive interaction between tryptophan and tyrosine with regard to the blood-brain barrier and coenzyme tetrahydrobiopterin. Mania may be due to the initial conditions of physical hyperactivity and hypofunctional 5-HTP-producing cells inducing increased dopamine. Depression may be due to the initial conditions of physical hypoactivity and hypofunctional 5-HTP-producing cells inducing decreased serotonin. Psychomotor excitation may be due to the initial conditions of physical hyperactivity and hyperfunctional 5-HTP-producing cells inducing increased serotonin and substantially increased dopamine. The hallucinatory-paranoid state may be due to the initial conditions of physical hypoactivity and hyperfunctional 5-HTP-producing cells inducing increased serotonin and dopamine.

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.

Shu­Yu capsule, a Traditional Chinese Medicine formulation, attenuates premenstrual syndrome depression induced by chronic stress constraint.

The present study aimed to investigate the therapeutic effect of the Shu-Yu capsule (SYC), a Traditional Chinese Medicine formulation, on premenstrual syndrome (PMS) depression and the ratio of glutamate (Glu) to γ-aminobutyric acid (GABA) in a rat model of PMS depression. Rats were randomly divided into a control group, model group, fluoxetine group, SYC group and saikosaponins (SS) group. The therapeutic effect of SYC was evaluated using a sucrose preference test (SPT), open field test (OFT) and body mass following four days of treatment. Hippocampal extracellular fluid was collected by microdialysis and the levels of Glu and GABA in the microdialysate were measured by high performance liquid chromatography. The results revealed that, compared with the control group, the sucrose preference coefficient (SC%), total score of OFT and body mass of the model group were significantly lower (P<0.01, P<0.05 and P<0.01, respectively). However, the sucrose preference coefficient, total score of OFT and body mass of the SYC group were all significantly increased compared with the model group (P<0.05). Furthermore, SYC inhibited the decrease of the Glu/GABA ratio in the hippocampus of rats with PMS depression. It was concluded that SYC effectively improved the symptoms of PMS depression, possibly by inhibiting the dysregulation of the Glu/GABA balance in the central nervous system.

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.