Daily Record Of Severity Of Problems Scores Research Articles

Effect of Dry Cupping on Physical Symptom of Headache in Premenstrual Syndrome among Females within 18-26 years : A Randomised Clinical Trial

BACKGROUND: Premenstrual syndrome or PMS are a group of psycho neuroendocrine condition whose cause is not known often experienced prior to menstruation. PMS symptoms are varied with prevalence of premenstrual headache of nearly 43%. Numerous evidences for management of PMS in general are available however literature on specific management of premenstrual headache is unavailable. OBJECTIVE: To determine the effect of dry cupping on physical symptom of headache in the premenstrual syndrome using Daily Record of Severity of Problems (DRSP), Headache Impact test (HIT-6) and Visual Analogue Scale (VAS) METHODS: Females within 18-26 years who complained of premenstrual headache and were willing to participate were included. Subjects were recruited and randomly divided into two groups. Outcome measures used were Daily Record of Severity of Problems (DRSP) and Headache Impact test (HIT-6). Visual Analogue Scale (VAS) was used pre and post intervention. Group A was given cervical traction whereas group B was given dry cupping and cervical traction. DRSP and HIT-6 were recorded for four cycles. RESULTS: The mean of demographic data suggested that both the group were homogenous at the baseline in terms of age and BMI. HIT-6 mean scores when compared from baseline to 2nd follow up for both the groups demonstrated statistically significant outcome. This improvement was maintained for over a period f two cycles in group B. DRSP and VAS mean scores were compared from baseline to post intervention showed high statistically significant improvement (p=0.0001) CONCLUSION: The study concludes that dry cupping is an effective tool for immediate to long term reduction of premenstrual headache symptoms.

The effect of Dioscorea esculenta powder on prostaglandin E2 and cytochrome c oxidase subunit 2 levels, menstrual pain, and premenstrual syndrome in young women: A randomized double-blind controlled trial.

Background Diosgenin, extracted from Dioscorea esculenta, has been reported to decrease prostaglandin E2 (PGE2) levels and any other inflammatory cytokine in rodents. However, it is still unclear whether D. esculenta intake suppressed PGE2 production and menstrual pain and premenstrual syndrome (PMS) in younger female. Aim This study aims to investigate the effect of D. esculenta intake on PGE2 and cytochrome c oxidase subunit 2 (COX-2) levels and on menstrual pain and PMS in young women. This is a randomized, double-blind, placebo-controlled, crossover study. Methods Ten healthy young females were administered either a placebo or D. esculenta (300 mg/day) for 4 weeks, followed by a 4-week washout period. Fasting blood sample was taken from the fingertips on the second day of menstrual cycle began and obtained 24h before the last D. esculenta to avoid acute effects. Participants then switched treatments for 4 weeks as a second trial. Plasma PGE2 and COX-2 levels were measured before and after each trial. The visual analogue scale (VAS), McGill pain questionnaire (MPQ), and Daily Record of Severity of Problems (DRSP) were also evaluated. The study was set and conducted from 2019 to 2020. Results PGE2 and COX-2 levels significantly decreased after D. esculenta intake compared to placebo (p = 0.038, p = 0.042 each). The VAS and DRSP scores were also significantly lower after D. esculenta intake (p = 0.046, p = 0.035 each). Conclusion Four-week D. esculenta intake suppressed PGE2 and COX-2 levels resulting in an improvement in PMS symptoms and menstrual pain in young women.

A DSM-5-based tool to monitor concurrent mood and premenstrual symptoms: the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS)

BackgroundDespite high co-morbidity between premenstrual dysphoric disorder and mood disorders, there is a gap of research-based tools to monitor concurrent premenstrual and mood symptoms. In this study, we developed a new DSM-5-based questionnaire to prospectively monitor concurrent premenstrual and mood symptoms.MethodsFifty-two females with bipolar or major depressive disorder, ages 16–45, were enrolled in the study. Participants completed two months of prospective symptom charting including the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS) and the Daily Record of Severity of Problems (DRSP). At the end of the prospective charting, participants also completed the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The MAC-PMSS was correlated with the DRSP, MADRS, HDRS and YMRS.ResultsAll individual items of the MAC-PMSS correlated strongly with the individual DRSP scores (all p < 0.001). The mood section of the MAC-PMSS also significantly correlated with MADRS (r = 0.572; p < 0.01), HDRS (r = 0.555; p < 0.01) and YMRS scores (r = 0.456; p < 0.01).ConclusionsThe MAC-PMSS is a reliable to tool to measure concurrent mood and premenstrual symptoms in women with mood disorders.

Evaluation of a natural S-equol supplement in treating premenstrual symptoms and the effect of the gut microbiota: An open-label pilot study.

AimPremenstrual syndrome causes disturbances in many women's daily activities. Isoflavones might cause changes in the estrogen cycle by their selective estrogen receptor modulator‐like activities. Equol, which is a metabolite of a soy isoflavone, has greater biological activity than other soy isoflavones. In this preliminary study, we aimed to examine the effect of a natural S‐equol supplement (SE5‐OH) on premenstrual symptoms. The gut microbiota has recently been suggested to play an important role in brain function in psychiatric disease, such as depression. Therefore, we further aimed to evaluate the relationship of the effect of SE5‐OH and the gut microbiota at preintervention.MethodsTwenty women who showed premenstrual symptoms and were nonequol producers were enrolled in an open‐label, single‐arm, clinical study in which they received oral SE5‐OH for two period cycles. The Daily Record of Severity of Problems (DRSP) total score was evaluated during the intervention cycles. Before taking SE5‐OH, fecal samples were obtained and subjected to terminal restriction fragment length polymorphism analysis.ResultsThe response rate to treatment (≥50% reduction from baseline in the DRSP total score) was 10.5%. Post hoc analysis showed a significant improvement in the change in the DRSP total score (P = .008) and DRSP scores for four core premenstrual dysphoric disorder symptoms. Multiple regression analysis showed that the percentage improvement of the DRSP total score was positively related to Bifidobacterium and negatively related to Clostridium cluster IV.ConclusionSE5‐OH supplementation may be an acceptable treatment for premenstrual symptoms. The intestinal microbiota may have an effect on SE5‐OH.

Progesterone Modulator May Offer PMDD Relief

Progesterone Modulator May Offer PMDD Relief

Biomarker Validation of a New Case Definition of Menstrual Cycle-Associated Syndrome (MCAS) Opinion Paper

There are different case definitions of premenstrual syndrome, one proposed by the American College of Obstetricians and Gynecologists (ACOG) and another based on the Daily Record of Severity of Problems (DRSP) scores. Here we review our recent findings indicating that the gold-standard methods to assess PMS, including ACOG, provide a high degree of false-negative findings. We propose a new case definition of the Menstrual Cycle-Associated Syndrome (MCAS), which is characterized by increased DRSP scores during the menstrual cycle and symptom that increases the week prior to the menses. The MCAS case definition was externally validated by diverse biomarkers including plasma levels of progesterone and estradiol, chemokines (e.g. CCL2, CCL5 and CCL11), epidermal growth factor, hydroperoxides, paraoxonase 1 activity and complement C4. These biomarkers as well as IgA responses to Gram-negative bacteria are significantly associated with the DRSP and its subdomains including depression, anxiety, and physiosomatic symptoms(fatigue, pain). In conclusion, we propose, a) to use the MCAS diagnosis as an indicant of menstrual cycle-related symptoms; and b) to examine the associations of the time series in the DRSP and its subdomains and those in biomarkers including distributed lag models. Aberrations in the uterine-chemokine-brain-axis underpin the pathophysiology of MCAS whereby suboptimal pre-ovulatory follicular development coupled with a relative corpus luteum insufficiency may drive increased chemokine production, lowered antioxidant defenses, neuro-oxidative stress pathways, and increased bacterial translocation. As such, we have delineated new drug targets for the treatment of MCAS. This opinion paper reviews new possible treatments that should be trialed in MCAS.

The role of immune and oxidative pathways in menstrual cycle associated depressive, physio-somatic, breast and anxiety symptoms: Modulation by sex hormones

ObjectiveTo examine whether 1) immune and nitro-oxidative stress (IO&NS) biomarkers are associated with premenstrual syndrome (PMS); and 2) changes in IO&NS biomarkers during the menstrual cycle (MC) are associated with PMS symptoms and plasma estradiol and progesterone. MethodsThis longitudinal study examined 41 women who completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days and assayed plasma levels of complement C3 and C4, highly sensitive C-reactive protein (hsCRP), haptoglobin (Hp), advanced oxidation protein products (AOPP), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), sulfhydryl (-SH) groups and the activity of paraoxonase (PON)1 at days 7 (D7), 14 (D14), 21 (D21) and 28 (D28) of the MC. MC Associated Syndrome (MCAS) was diagnosed when the summed DRSP score during the MC is >0.666 percentile. ResultsAll biomarkers, except hsCRP, showed significant alterations during the MC. Arylesterase (AREase) was lowered at D28, while LOOH increased at D14 and C4 at D21 in MCAS. Total DRSP scores were predicted by the combined effects of C4 (positively) and AREase and malondialdehyde (MDA) (both inversely associated). Progesterone lowered levels of LOOH, AOPP and C3 and estradiol lowered levels of Hp while both sex hormones increased 4-(chloromethyl)phenyl acetate (CMPA)ase and AREase activities and levels of -SH groups. ConclusionPMS/MCAS is not accompanied by a peripheral inflammatory response. Lowered MDA and antioxidant defenses and increased C4 may play a role in MC symptoms while sex hormones may have a protective effect against oxidative stress toxicity.

The uterine-chemokine-brain axis: menstrual cycle-associated symptoms (MCAS) are in part mediated by CCL2, CCL5, CCL11, CXCL8 and CXCL10

ObjectiveTo examine associations between chemokines and menstrual cycle associated symptoms (MCAS). MethodsForty-one women completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days of the menstrual cycle. MCAS is diagnosed when the total daily DRSP score during the menstrual cycle is > 0.666 percentile. We assayed plasma CCL2, CCL5, CCL11, CXCL8, CXCL10, EGF, IGF-1, and PAI-1 at days 7, 14, 21 and 28 of the menstrual cycle. ResultsCCL2, CCL5, CCL11 and EGF are significantly higher in women with MCAS than in those without. Increased CCL2, CXCL10, CXCL8, CCL11 and CCL5 levels are significantly associated with DRSP scores while CCL2 is the most significant predictor explaining 39.6% of the variance. The sum of the neurotoxic chemokines CCL2, CCL11 and CCL5 is significantly associated with the DRSP score and depression, physiosomatic, breast-craving and anxiety symptoms. The impact of chemokines on MCAS symptoms differ between consecutive weeks of the menstrual cycle with CCL2 being the most important predictor of increased DRSP levels during the first two weeks, and CXCL10 or a combination of CCL2, CCL11 and CCL5 being the best predictors during week 3 and 4, respectively. DiscussionThe novel case definition “MCAS” is externally validated by increased levels of uterus-associated chemokines and EGF. Those chemokines are involved in MCAS and are regulated by sex hormones and modulate endometrium functions and brain neuro-immune responses, which may underpin MCAS symptoms. As such, uterine-related chemokines may link the uterus with brain functions via a putative uterine-chemokine-brain axis.

Assessment of N-acetylcysteine as an Alternative for the Treatment of the Premenstrual Dysphoric Disorder: A Randomized Clinical Trial

Background: Premenstrual dysphoric disorder (PMDD) is a common condition affecting females' quality of life in a significant negative manner. Verities of medical treatments have been investigated for whether the prevention or treatment of this condition with uncertain outcomes. Currently, evidence has shown the role of oxidant and antioxidant agents in the etiology of PMDD. N-acetylcysteine (NAC) is an anti-inflammatory and antioxidant agent that we have aimed to assess its efficacy for the treatment of PMDD, and compare it with fluoxetine, as one of the choice treatment of this disorder.&#x0D; Methods: The current randomized clinical trial has been conducted on 119 childbearing females, randomly divided into three groups of either treatment with 10 mg of fluoxetine twice daily or 450 mg of NAC twice daily or placebo in 2016-2018. The agents were administered daily for two weeks within the initiation of menstruation cycle for two menstruation cycles. The questionnaires of Hamilton and daily record of severity of problems (DRSP) were filled before and following the interventions for groups, and the results were compared.&#x0D; Results: The baseline DRSP and Hamilton scores were not statistically different among the three groups (P&gt;0.05) while by the end of the study all of the groups presented significantly improved scores (P&lt;0.001). Comparison of three groups revealed remarkable inferiority of placebo to the other two groups (P&lt;0.05) while no statistical difference was found between N-acetylcysteine with fluoxetine in terms of neither Hamilton (P:0.12) nor DRSP scores (P:0.75).&#x0D; Conclusion: Findings of our study are in favor of NAC use for the treatment of PMDD. Further studies with larger sample size and elongated duration of treatment and follow-ups are strongly recommended.&#x0D; J Pharm Care 2019; 7(4): 94-99

The Uterine-Chemokine-Brain Axis: Menstrual Cycle-Associated Symptoms (MCAS) Are in Part Mediated by CCL2, CCL5, CCL11, CXCL8 and CXCL10

Objective: To examine associations between chemokines and menstrual cycle associated symptoms (MCAS). Methods: Forty-one women completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days of the menstrual cycle. is diagnosed when the total daily DRSP score during the menstrual cycle is > 0.666 percentile. We assayed plasma CCL2, CCL5, CCL11, CXCL8, CXCL10, EGF, IGF-1, and PAI-1 at days 7, 14, 21 and 28 of the menstrual cycle. Results: CCL2, CCL5, CCL11 and EGF are significantly higher in women with than in those without. Increased CCL2, CXCL10, CXCL8, CCL11 and CCL5 levels are significantly associated with DRSP scores while CCL2 is the most significant predictor explaining 39.6% of the variance. The sum of the neurotoxic chemokines CCL2, CCL11 and CCL5 is significantly associated with the DRSP score and depression, physiosomatic, breast-craving and anxiety symptoms. The impact of chemokines on symptoms may differ between consecutive weeks of the menstrual cycle with CCL2 being the most important predictor of increased DRSP levels during the first two weeks, and CXCL10 or a combination of CCL2, CCL11 and CCL5 being the best predictors during week 3 and 4, respectively. Discussion: The novel case definition MCAS is externally validated by increased levels of uterus-associated chemokines and EGF. Those chemokines are involved in and are regulated by sex hormones and modulate endometrium functions and brain neuro-immune responses, which may underpin symptoms. As such, uterine-related chemokines may link the uterus with brain functions via a putative uterine-chemokine-brain axis. Funding Statement: This research has been supported by 1) the Ratchadaphiseksomphot Fund, Faculty of Medicine, Chulalongkorn University, grant number RA61/016; 2) Chulalongkorn University; Government Budget; and 3) the Ratchadaphiseksomphot Fund, Chulalongkorn University. Declaration of Interests: The authors have no conflict of interest with any commercial or other association in connection with the submitted article. Ethics Approval Statement: The study was approved by the Ethics Committee of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (IRB No.611/60, COA No. 1111/2017). Written informed consent was obtained from all participants prior to the study.

The menstrual cycle may not be limited to the endometrium but also may impact gut permeability.

To examine associations between IgA responses to Gram-negative gut commensal bacteria and peri-menstrual symptoms and sex hormone levels during the menstrual cycle in women with and without premenstrual symptoms. Forty women aged 18-45 years completed the Daily Record of Severity of Problems (DRSP) during all 28 consecutive days of the menstrual cycle. We assayed, in plasma, IgA responses to six Gram-negative bacteria, that is, Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii, Klebsiella pneumoniae, Pseudomonas putida and Citobacter koseri, progesterone and oestradiol at days 7, 14, 21 and 28 of the menstrual cycle. Significant changes in Δ (actual - 1 week earlier) IgA to lipopolysaccharides (LPS) of the six Gram-negative bacteria during the menstrual cycle were observed with peak IgA levels at T4 (day 28) and lows at T1 or T2 (day 7 or 14). The ΔIgA changes in H. alvei, M. Morganii, P. putida during the menstrual cycle were significantly and positively associated with changes in the total DRSP score, and severity of physio-somatic, anxiety and breast-craving, but not depressive, symptoms. The changes in IgA responses to LPS were largely predicted by changes in progesterone and steady-state levels of progesterone averaged over the luteal phase. Menstrual cycle-associated changes in IgA directed against LPS and by inference bacterial translocation may be driven by the effects of progesterone on transcellular, paracellular and vascular pathways (leaky gut) thereby contributing to the severity of physio-somatic and anxiety symptoms as well as fatigue, breast swelling and food cravings.

Remote intervention using smartphone for rural women suffering from premenstrual syndrome: A propensity score matched analysis.

Timely treatment of premenstrual syndrome (PMS) is not always available for rural women, because the local medical resources are insufficient. The efficacy of remote intervention by smartphone on PMS has not been confirmed.A retrospective analysis was performed on rural PMS patients between January 2014 and December 2015. After a propensity score matched analysis, 60 patients were enrolled and evenly divided into remote group and outpatient group. Multidisciplinary therapy including cognitive-behavioral therapy (CBT), oral medication, and physical exercise education was used individually, in accordance with their symptoms evaluated by Daily Record of Severity of Problems (DRSP) questionnaire. Patients in remote group utilized WeChat software by smartphone for therapy guidance, while those in outpatient group attended face-to-face interview. Their DRSP scores in 5 new menstrual cycles after therapy were recorded. Then, they were followed up for 1 year.Total DRSP scores of the cases in both groups after initial intervention were less than those before therapy (P < .001), without group difference (P > .05). However, patients in remote group indicated a higher satisfactory rate than the outpatient group (P = .03). On the 1-year follow up, patients in both groups demonstrated similar DRSP scores (P = .07), but the satisfactory rate in remote group was encouragingly higher than that in the outpatient group (P = .02).The efficacy of remote intervention using smartphone on PMS is noninferior to traditional outpatient visits. Nevertheless, high-quality trials are needed.

Semi-Individualized Homeopathy Add-On Versus Usual Care Only for Premenstrual Disorders: A Randomized, Controlled Feasibility Study.

Premenstrual syndrome and premenstrual dysphoric disorder (PMS/PMDD) bother a substantial number of women. Homeopathy seems a promising treatment, but it needs investigation using reliable study designs. The feasibility of organizing an international randomized pragmatic trial on a homeopathic add-on treatment (usual care [UC] + HT) compared with UC alone was evaluated. A multicenter, randomized, controlled pragmatic trial with parallel groups. The study was organized in general and private homeopathic practices in the Netherlands and Sweden and in an outpatient university clinic in Germany. Women diagnosed as having PMS/PMDD, based on prospective daily rating by the daily record of severity of problems (DRSP) during a period of 2 months, were included and randomized. Women were to receive UC + HT or UC for 4 months. Homeopathic medicine selection was according to a previously tested prognostic questionnaire and electronic algorithm. Usual care was as provided by the women's general practitioner according to their preferences. Before and after treatment, the women completed diaries (DRSP), the measure yourself concerns and well-being, and other questionnaires. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. In Germany, the study could not proceed because of legal limitations. In Sweden, recruitment proved extremely difficult. In the Netherlands and Sweden, 60 women were randomized (UC + HT: 28; UC: 32), data of 47/46 women were analyzed (ITT/PP). After 4 months, relative mean change of DRSP scores in the UC + HT group was significantly better than in the UC group (p = 0.03). With respect to recruitment and different legal status, it does not seem feasible to perform a larger, international, pragmatic randomized trial on (semi-)individualized homeopathy for PMS/PMDD. Since the added value of HT compared with UC was demonstrated by significant differences in symptom score changes, further studies are warranted.

Larger volume and different functional connectivity of the amygdala in women with premenstrual syndrome.

To assess structural and functional changes of the amygdala due to premenstrual syndrome (PMS) using magnetic resonance imaging (MRI). Twenty PMS patients and 21 healthy control (HC) subjects underwent a 6-min resting-state fMRI scan during the luteal phase as well as scanning high-resolution T1-weighted images. Subcortical amygdala-related volume and functional connectivity (FC) were estimated between the two groups. Each subject completed a daily record of severity of problems (DRSP) to measure the severity of clinical symptoms. Greater bilateral amygdalae volumes were found in PMS patients compared with HC subjects, and PMS patients had increased FC between the amygdala and certain regions of the frontal cortex (e.g. medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), right precentral gyrus), the right temporal pole and the insula, as well as decreased FC between the bilateral amygdalae and the right orbitofrontal cortex and right hippocampus. The strength of FC between the right amygdala and right precentral gyrus, left ACC and left mPFC were significantly and positively correlated with DRSP scores in PMS patients. Our findings may improve our understanding of the neural mechanisms involved in PMS. • Functional and structural MRI used to explore amygdala in PMS patients. • Aberrant amygdala structural and functional connectivity were found in PMS patients. • Amygdala strength FC was positively correlated with individual clinical symptom scores.

Treatment of Premenstrual Breakthrough of Depression With Adjunctive Oral Contraceptive Pills Compared With Placebo.

Two-thirds of women with depressive disorders report reemergence of depression premenstrually, or premenstrual exacerbation (PME), despite effective treatment of the underlying mood disorder during the remainder of the cycle. There is a paucity of studies that rigorously assess treatments targeting PME. Open-label data suggest that augmentation of antidepressants with the oral contraceptive pill (OCP) drospirenone and ethinyl estradiol (DRSP/EE) improves depressive symptoms that break through treatment premenstrually. We now report results of a randomized placebo-controlled OCP augmentation trial. Women with unipolar depressive disorders in remission on stable antidepressant doses with a 30% increase in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from the follicular to luteal phase were randomized to double-blind augmentation of antidepressant with either DRSP/EE or placebo for 2 months. The MADRS and Daily Record of Severity of Problems (DRSP) measures were anchored to the menstrual cycle phase. Of 32 women randomized, 25 (n = 12 DRSP/EE, n = 13 placebo) completed the trial. Premenstrual MADRS scores declined by a median of 43.6% and 38.9% (P = 0.59), and premenstrual DRSP scores declined by a median of 23.5% and 20.9% (P = 0.62) in the DRSP/EE and placebo groups, respectively. There was a trend toward greater improvement in premenstrual DRSP scores for women with fewer lifetime depressive episodes (r = -0.40, P = 0.06). Findings from this small randomized trial suggest that OCP augmentation of antidepressants may not be effective for treating premenstrual breakthrough of depression. Future studies should target women established to have hormonal sensitivity prior to antidepressant therapy and those with fewer lifetime depressive episodes.

Hippocampal fractional amplitude of low-frequency fluctuation and functional connectivity changes in premenstrual syndrome.

To investigate differences in hippocampal activity between premenstrual syndrome (PMS) patients and healthy controls, to elucidate the neural mechanisms of PMS. Twenty female patients with PMS (PMS group) and 21 healthy controls (HC group) underwent a single-shot gradient-recalled echo planar imaging (EPI) sequence scan during the luteal phase in 3.0 Tesla MRI. Spontaneous neural activity in hippocampus (HIPP) was measured by fractional amplitude of low-frequency fluctuation (fALFF). Functional connectivity (FC) was used to examine the neural networks of PMS patients by selecting the abnormal HIPP as the seed region. All participants completed a daily record of severity of problems (DRSP) questionnaire to measure the severity of clinical symptoms. Results from a two-sample t-test showed increased left HIPP fALFF in the PMS group compared with the HC group (P = 0.042), while there was no between-group difference of fALFF in the right HIPP (P = 0.1011). A secondary analysis using a two-sample t-test with the left HIPP as the seed region, the results revealed that the PMS group exhibited increased FC between the left HIPP and left medial prefrontal cortex (mPFC), left posterior cingulate cortex (PCC), right middle cingulate cortex (MCC), and bilateral precentral cortex (PC), while decreased FC between the left HIPP and right orbitofrontal cortex (OFC). Moreover, the PMS group exhibited higher DRSP scores, which were positively correlated (r = 0.64, P = 0.003) with FC between the left HIPP and mPFC during the luteal phase. Altered spontaneous neural activity and connectivity of left HIPP may be involved in PMS. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:545-553.

Altered fractional amplitude of low frequency fluctuation in premenstrual syndrome: A resting state fMRI study

BackgroundPremenstrual syndrome (PMS) is becoming highly prevalent among female and is characterized by emotional, physical and behavior symptoms. Previous evidence suggested functional dysregulation of female brain was expected to be involved in the etiology of PMS. The aim of present study was to evaluate the alterations of spontaneous brain activity in PMS patients based on functional magnetic resonance imaging (fMRI). Methods20 PMS patients and 21 healthy controls underwent resting-state fMRI scanning during luteal phase. All participants were asked to complete a prospective daily record of severity of problems (DRSP) questionnaire. ResultsCompared with healthy controls, the results showed that PMS patients had increased fALFF in bilateral precuneus, left hippocampus and left inferior temporal cortex, and decreased fALFF in bilateral anterior cingulate cortex (ACC) and cerebellum at luteal phase. Moreover, the DRSP scores of PMS patients were negatively correlated with the mean fALFF in ACC and positively correlated with the fALFF in precuneus. Limitations(1) the study did not investigate whether or not abnormal brain activity differences between groups in mid-follicular phase, and within-group changes. between phases.(2) it was relatively limited sample size and the participants were young; (3) fALFF could not provide us with more holistic information of brain network;(4) the comparisons of PMS and premenstrual dysphoric disorder (PMDD) were not involved in the study. ConclusionsThe present study shows abnormal spontaneous brain activity in PMS patients revealed by fALFF, which could provide neuroimaging evidence to further improve our understanding of the underlying neural mechanism of PMS.

Treatment of premenstrual dysphoric disorder with the GABAA receptor modulating steroid antagonist Sepranolone (UC1010)—A randomized controlled trial

ContextAllopregnanolone is a metabolite from progesterone and a positive modulator of the GABAA receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models. ObjectiveThe objective was to test whether inhibition of allopregnanolone by treatment with the GABAA modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD. DesignThis was an explorative randomized, double-blind, placebo-controlled study. SettingSwedish multicentre study with 10 centers. ParticipantsParticipants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott’s algorithm. InterventionSubjects were randomized to treatment with UC1010 (10 or 16mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle. Outcome measuresThe primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life). Results26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p=0.041) and borderline significance (p=0.051) for the sum of Negative mood score.Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n=60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p=0.006), and for sum of Negative mood score (p=0.003) and impairment (p=0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study. ConclusionsThis explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

Abnormal Spontaneous Brain Activity in Women with Premenstrual Syndrome Revealed by Regional Homogeneity.

Background: Previous studies have revealed that the etiologies of premenstrual syndrome (PMS) refer to menstrual cycle related brain changes. However, its intrinsic neural mechanism is still unclear. The aim of the present study was to assess abnormal spontaneous brain activity and to explicate the intricate neural mechanism of PMS using resting state functional magnetic resonance imaging (RS-fMRI).Materials and Methods: The data of 20 PMS patients (PMS group) and 21 healthy controls (HC group) were analyzed by regional homogeneity (ReHo) method during the late luteal phase of menstrual cycle. In addition, all the participants were asked to complete a daily record of severity of problems (DRSP) questionnaire.Results: Compared with HC group, the results showed that PMS group had increased ReHo mainly in the bilateral precuneus, left inferior temporal cortex (ITC), right inferior frontal cortex (IFC) and left middle frontal cortex (MFC) and decreased ReHo in the right anterior cingulate cortex (ACC) at the luteal phase. Moreover, the PMS group had higher DRSP scores, and the DRSP scores positively correlated with ReHo in left MFC and negatively correlated with ReHo in the right ACC.Conclusion: Our results suggest that abnormal spontaneous brain activity is found in PMS patients and the severity of symptom is specifically related to the left MFC and right ACC. The present findings may be beneficial to explicate the intricate neural mechanism of PMS.

Symptom-Onset Dosing of Sertraline for the Treatment of Premenstrual Dysphoric Disorder: A Randomized Clinical Trial.

Serotonin reuptake inhibitors (SRIs) are efficacious treatments for premenstrual dysphoric disorder (PMDD) when given daily or for half of the menstrual cycle during the luteal phase. Preliminary studies suggest that SRI treatment can be shortened to the interval from symptom onset through the beginning of menses. To determine the efficacy of symptom-onset dosing with the SRI sertraline hydrochloride for treatment of PMDD. A double-blind, placebo-controlled, multisite, parallel-group randomized clinical trial conducted September 1, 2007, to February 29, 2012, at 3 university medical centers. In all, 252 women with PMDD started treatment at symptom onset and continued until the first few days of menses for 6 menstrual cycles. Intent-to-treat analyses were performed February 28, 2014, through April 21, 2015. Placebo or sertraline hydrochloride, 50 to 100 mg/d, during the symptomatic interval. Premenstrual Tension Scale (PMTS) score was the primary outcome measure (score range, 0-36; 36 indicates most severe score). Secondary outcome measures included the Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C) (score range, 0-84; 84 indicates most severe score), Daily Record of Severity of Problems (DRSP) (total and subscale scores; higher scores indicate most severe problems), Clinical Global Impression (CGI) scales (score range, 1-7; 7 indicates most severe symptoms and least improvement), and Michelson SSRI (Selective SRI) Withdrawal Symptoms Scale scores (range, 0-51; higher scores indicate more severe withdrawal symptoms). Among the participants, 125 with PMDD were randomized to sertraline, and 127 to placebo. At baseline the mean (SD) PMTS scores for sertaline and placebo were 22.3 (4.8) and 21.4 (4.5), respectively, which declined to 11.7 (6.8) and 12.0 (6.9), respectively; group mean difference, 1.88 (95% CI, 0.01-3.75; P = .06). The mean (SD) estimated difference in IDS-C scores between baseline (35.4 [10.7] for sertraline; 32.8 [10.4] for placebo) and the end point (15.3 [10.7] for sertraline; 17.8 [11.0] for placebo) favored the sertraline group by 5.14 (95% CI, 1.97-8.31) points (P = .02). Compared with the placebo group, those assigned to sertraline showed greater improvement on the total DRSP score (estimated mean difference, 1.09 [95% CI, 0.96-1.25] points; P = .02) and Anger/Irritability DRSP subscale score (1.22 [95% CI, 1.05-1.41] points; P < .01) and were more likely to respond to treatment (77 of 115 patients [67.0%] for sertraline and 65 of 124 [52.4%] for placebo; χ21 = 5.23; P = .02). The mean (SD) number of symptomatic days before treatment diminished over time (sertraline, -0.7 [3.4] days; placebo, -1.0 [3.2] days), with no group differences in symptomatic days or the Michelson SSRI Withdrawal Symptoms Scale. Depending on the symptom scale, women with PMDD may or may not benefit from SRI treatment during the interval from the onset of premenstrual symptoms through the first few days of menses. Abrupt treatment cessation was not associated with discontinuation symptoms. clinicaltrials.gov Identifier: NCT00536198.