The Efficacy and Safety of Modified Xiaoyao San for Perimenopausal Syndrome (PMS): A Systematic Review and Meta-Analysis

Objectives: To assess the efficacy and safety of modified Xiaoyao San (XYS) for treating Perimenopausal syndrome (PMS). Methods: Literature searches were carried out on PubMed, Cochrane Library, CNKI Database, Chinese Biomedical Literature Database, Wan Fang Database, and VIP Database up to December 2018. Hand search for further references was conducted. Study selection, data extraction, quality assessment, and data analyses were performed as request of the Cochrane standards. Results: Nine publications in total were suitable for inclusion. There was evidence that modified XYS was tested to be more effective in improving overall symptoms compared with HRT (odds ratio 3.50, 95% CI 2.56 to 4.78). Whereas HRT was more sensitive and direct in decreasing FSH (WMD 6.69, 95% CI 5.60 to 9.52) and LH (WMD 7.00, 95% CI, 5.75 to 8.25) in comparison with XYS group. It was also strongly supported that XYS had less adverse effect than HRT (odds ratio 0.07, 95% CI 0.05 to 0.10). Conclusion: Modified XYS might be more effective and safer in treatment of perimenopausal syndrome. However, due to poor methodological quality in the majority of included studies, the potential benefit and safety about XYS need to be confirmed in rigorously designed, multi-centre, and large-scale trials.

The Prevalence and Symptoms of Premenstrual Syndrome under Examination

Introduction: Premenstrual Syndrome (PMS) is a common disorder in childbearing age. Based on different definitions, it is accompanied with specific annoying symptoms that clearly emerge after ovulation and decrease or end with the onset of menstruation. Methods: The present study aimed to determine the prevalence of premenstrual syndrome in university students of Sistan and Baluchestan University (Iran) in the academic year 2013-2014. Two hundred and one female university students living in dormitories were randomly selected. The subjects completed two questionnaires of Demographic Information and Symptom Assessment based on the criteria of ACOG and DSM-IV. Results: According to the mentioned criteria, “36.3%” of subjects suffered from Premenstrual Dysphoric Disorder (PMDD) and “85.6%” of subjects indicated the symptoms of PMS. The severity of PMS in 14(%7) subjects was high. Of 86 and 72 subjects “42.8%” and “35.8%” was moderate respectively, it was mild. Among university students, the most common mood symptom (emotional) and somatic symptom (physical) were fatigue and lethargy and abdominal pain (“72.6%” and “62.7%”, respectively). PMS was significantly related to dysmenorrhea and severity of menstrual pain (p < 0.05). Conclusion: Given the high prevalence of this syndrome and its effect on various aspects of life, we highly recommend informing young individuals through books, workshops and media in order to identify the symptoms, provide information about methods of control and treatment of this syndrome, and apply non-interventional treatments and methods to reduce the symptoms.

Is Premenstrual Syndrome a Uterine Inflammatory Disease? Retrospective Evaluation of an Etiologic Approach

Objective: To retrospectively evaluate the efficacy of local uterine antibiotic and anti-inflammatory injections combined with cryotherapy for the treatment of severe Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD). To validate the hypothesis of a uterine infectious/inflammatory etiology of PMS/PMDD. Methods: Clinical files of 161 women sequentially treated from September 1995 to April 2005, were collected for study. A subset of 148 patients (mean: 36.7 ± 7.8 years, range: 20.1 - 53.8 years) were eligible for statistical analysis. The ten most relevant PMS symptoms, namely depression, irritability, anxiety, fatigue, headache, edema, breast tenderness, abdominal bloating, pelvic pain and dysmenorrhea, were self-rated before and three menstrual cycles after treatment, using a 0 to 5 scale. The treatment consisted of cervical stromal antibiotic/anti-inflammatory injections combined with intracervical cryotherapy. Scores were compared using non-parametric tests for matched samples. Results: Before treatment, mean severity scores for the 10 symptoms were 3.97 ± 1.17, 4.26 ± 0.88, 3.41 ± 1.23, 3.91 ± 0.94, 3.35 ± 1.71, 2.28 ± 1.69, 2.13 ± 1.63, 4.51 ± 0.63, 2.28 ± 1.30, and 2.28 ± 1.88, respectively. Mean values after treatment were 0.54 ± 0.91, 0.51 ± 0.91, 0.32 ± 0.70, 0.42 ± 0.74, 0.43 ± 0.96, 0.22 ± 0.53, 0.39 ± 0.73, 1.01 ± 0.94, 0.28 ± 0.69, and 0.44 ± 0.92. All tests were statistically significant (p < 0.01). Conclusion: Both PMS physical and psycho-affective symptoms respond to local anti-inflammatory and antibiotic treatment of the uterus, showing a stable improvement after the treatment has ended. The results of this study suggest that the clinical pattern of PMS can be explained as an inflammatory mediated response to uterine infectious or traumatic insults. Further evidence is urgently needed in order to validate this innovative approach for widespread use in severe PMS/ PMDD cases.

An exploratory pilot of factors associated with premenstrual syndrome in minority women

Purpose:This investigation explored factors associated with premenstrual syndrome(PMS)in minority women,and compared the response of minority and non-minority women supplemented with omega-3 fatty acids(FA)in the form of fish oil.Methods:This descriptive,correlational,retrospective pilot was a secondary data analysis.Participants consuming 2 g of fish oil/d(n=15)in the larger study were included.The Moos Menstrual Distress Questionnaire(MMDQ)was assessed monthly for two months to acquire a mean baseline MMDQ score.The total sample was stratified to evaluate racial variations in PMS symptoms(non-minority,n=7;minority,n=8).MMDQ score at 5 months was compared to the mean baseline score within each group.Results:Fish oil supplementation significantly reduced PMS symptoms in both groups(nonminority p=0.002;minority p=0.046)with a large effect of 1.4 for both groups.Mean MMDQ total scores were not significantly different between groups at 5 months.Conclusions:This pilot evidence of improved PMS symptoms in minority and non-minority groups related to fish oil supplementation supports a universal treatment approach and highlights need for a larger-scale investigation.

OBSERVATION ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE THERAPY FOR SIMPLE OBESITY COMPLICATED WITH PREMENSTRUAL TENSION SYNDROME

Objective: To observe the therapeutic effect of acupuncture therapy in the treatment of simple obesity complicated with premenstrual tension syndrome. Methods: A total of 39 cases of simple obesity complicated with premenstrual tension were treated by combination of body acupuncture and otoacupuncture based on syndrome-differentiation of traditional Chinese medicine (TCM). Symptoms, physical signs, obesity indexes and cumulative scores of clinical disease-syndrome before and after treatment were analyzed and compared. Results: After one, two and three courses of treatment, the effective rates were 69.23%, 79.49% and 87.18% respectively. Conclusion: Acupuncture therapy works well in the treatment of simple obesity with concurrent premenstrual tension syndrome.

ACUPUNCTURE TREATMENT OF FEMALE OBESITY COMPLICATED WITH PREMENSTRUAL TENSION SYNDROME

Objective： To explore mechanisms of acupuncture for the treatment of obesity complicated with prernenstrual tension syndrome （PTS）. Methods： By means of syndrome-differentiation, 45 female simple obese （SO） patients with PTS （SO＋ PTS group and 35 simple obesity patients （SO group） were treated with body acupuncture combined with ear acupuncture. Thirtythree normal women subjects were assigned to control group. Changes in symptoms, signs, obesity index, clinical indices of disease and syndrome, equilibrium index of the vegetative nervous system （Y value）, blood estradiol （E2）, progesterone （P）, aldosterone （Aid） and lipid levels were detected and compared before and after the treatment. Results： Before acupuncture treatmerit, the obesity index, clinical indices of disease and syndrome, Y value, E2/P ratio and Aid in these patients were obviously increased, and E2 and P levels decreased. After the treatment, the body weight of the patients was reduced, and the increased obesity index, clinical indices of diseases and syndromes, Y value, E2/P ratio and Aid were markedly lowered （P〈0.05, or P 〈 0.01）, and the decreased E2 and P levels elevated significantly （P〈 0.01）. Conclusion： Acupuncture exerts favorable regulative function on clinical indices of disease and syndrome, Y value, E2, P, Aid, lipid and E2/P in obese patients with PTS, which may be related to its resultant improvement of the functions of the hypothalamo-pituitary-gonedal axis, hypothalamo-pituitary-adrenal axis and the vegetative nervous system.

Effectiveness and safety of Jiawei Xiaoyao pill(加味逍遥丸)in the treatment of premenstrual syndrome(liver depression,spleen deficiency,and blood-heat syndrome):a multi-center,randomized,placebo-controlled trial

OBJECTIVE:To investigate the effectiveness and safety of Jiawei Xiaoyao pill(加味逍遥丸,JXP)in the treatment of symptoms associated with premenstrual syndrome(PMS).METHODS:A total of 144 regularly menstruating women with PMS were recruited at 8 sites in China from August 2017 to December 2018,and randomized to receive either a JXP or a matching placebo(12 g/d,6 g twice a day)for 3 menstrual cycles.The primary indicator was the reduced Daily Record of Severity of Problems(DRSP)scores in the luteal phase after 3 months of treatment.The safety outcomes included clinical adverse events(AEs),adverse reactions(ARs),changes in vital signs,and laboratory tests.RESULTS:JXP surpassed the placebo in reducing DRSP scores(psychological/somatic dysfunction)in the luteal phase over 3 menstrual cycles of treatment(PFAS=0.002,PPPS=0.001).Additionally,there were no significant differences in the incidence of AEs,severe AEs,withdrawal due to AEs and ARs between the two groups(all P>0.05),and no clinically significant adverse medical events related to the test drug observed.CONCLUSIONS:JXP was superior to the placebo in relieving the symptoms associated with PMS,which signified that JXP may be effective,safe,and welltolerated as an alternative therapy.

Efficacy and Safety of Ganyushu Granule in Treatment of Premenstrual Syndrome with Gan(Liver)Depression and Qi Stagnation Syndrome:A Randomized,Double-Blind,Multicenter,Phase-ⅡClinical Trial

Objective:To confirm the efficacy and safety of Ganyushu Granule(GYSG)in treating premenstrual syndrome(PMS)in patients with Gan(Liver)depression and qi stagnation syndrome(GDQSS)and determine its effective dosage.Methods:From June 2018 to March 2021,a total of 240 PMS women with GDQSS were included and randomly divided into 3 groups in a 1:1:1 ratio using central block randomization:high-dose GYSG group(n=78,GYSG 2 packs/time),low-dose GYSG group(n=82,GYSG and its simulant 1 pack/time),and placebo group(n=80,GYSG simulant 2 packs/time).Treatment with GYSG or placebo was given thrice daily and for up to 3 menstrual cycles.Primary outcomes were PMS diary(PMSD)score and premenstrual tension syndrome self-rating scale(PMTS).Secondary outcomes were Chinese medicine(CM)syndrome efficacy.PMSD,PMTS,and efficacy of CM were evaluated with menstrual cycles during the treatment period.Outcome indicators were analyzed after each menstrual cycle.All analyses were performed using an intention-to-treat method,and clinical safety was assessed.Results:Of the 216 patients included in the effectiveness analysis,70,75,and 71 patients were in the high-,low-dose GYSG,and placebo groups,respectively.From the 2nd treatment cycle,the change in PMSD scores in the high-and low-dose groups was lower than that in the placebo group(P<0.05).PMTS scores in the high-dose GYSG group after the 1st treatment cycle was lower than that in the placebo group(P<0.05),while after the 3rd treatment cycle,that in the low-dose group was lower than that in the placebo group(P<0.05).After the 2nd treatment cycle,the high-dose GYSG group had the best CM syndrome efficacy(P<0.05).No serious adverse reactions were reported.Conclusions:GYSG was safe and well-tolerated at both doses for treating PMS patients with GDQSS.High-dose GYSG might be the optimal dose for a phaseⅢtrial.

经前舒颗粒对PMS肝气郁证模型大鼠下丘脑MAOA和MAOB表达水平的影响

目的通过研究PMS肝气郁证模型大鼠下丘脑MAOA和MAOB基因的表达,探讨PMS肝气郁证的微观发病机制及中药经前舒颗粒的作用靶点。方法束缚法制备PMS肝气郁证模型大鼠,用经前舒颗粒干预治疗,运用半定量RT-PCR和Western Blotting方法检测正常组、模型组、给药组大鼠下丘脑区MAOA、MAOB mRNA及其蛋白表达水平;通过单因素方差分析及LSD法统计数据。结果与正常组相比,PMS肝气郁证模型组大鼠MAOA mRNA在下丘脑表达显著升高(P<0.05),蛋白表达极显著升高(P<0.01);MAOB mRNA及蛋白在下丘脑表达均无统计学差异(P>0.05);给药组与模型组相比,MAOA mRNA在下丘脑表达降低(P<0.05),蛋白表达显著降低(P<0.01);MAOB mRNA及蛋白在下丘脑表达均无统计学差异(P>0.05);给药组与正常组相比,MAOA、MAOB mRNA及蛋白在大鼠下丘脑中表达均无统计学差异(P>0.05)。结论模型组大鼠与正常组大鼠相比,下丘脑MAOA基因表达升高,通过经前舒颗粒干预后,恢复正常。说明MAOA基因与PMS肝气郁证相关,并且可能是经前舒颗粒治疗该证的作用机制之一。

深圳市福田区育龄女职工经前期综合征(PMS)的初步调查

目的:了解深圳市福田区育龄女职工经前期综合征(PMS)的发生情况及影响因素。方法:对深圳市福田区企事业单位19～40岁的育龄女职工860人进行问卷调查,了解PMS的发生情况以及可能的影响因素。结果:问卷有效率为94.0%(808人),PMS的患病率为60.02%(485人),其中轻度占64.95%(315人),中度占30.31%(147人),重度占4.74%(23人);PMS发生率较高的症状为精神症状,如情绪不稳定、易激怒,其次为躯体症状,如头痛、乳房胀痛、腹胀腹泻等,也有少数有行为改变症状。文化程度高者的PMS患病率高于文化程度低者(P<0.05)。结论:PMS是育龄妇女较常见的疾病,应引起医务工作者的关注,并应针对妇女生理特点采取综合性干预措施。

白香丹对PMS肝气逆证模型大鼠GABA_BR亚基分布及表达的影响

目的观察白香丹对经前期综合征(PMS)肝气逆证模型大鼠额区和下丘脑中γ-氨基丁酸(GABA)B1受体(GBR1)、γ-氨基丁酸B2受体(GBR2)分布及表达的影响,探讨白香丹对PMS肝气逆证的干预机制。方法通过旷场实验和阴道涂片法筛选健康雌性Wistar大鼠进入实验,采用电刺激法复制PMS肝气逆证大鼠模型,用免疫荧光双标记技术检测GBR1和GBR2在额区和下丘脑中的表达。结果与正常对照组大鼠比较,模型组大鼠垂直得分、水平得分和总分均显著增加(P<0.01),GBR1和GBR2蛋白在额区和下丘脑中的表达水平降低(P<0.01);与模型组大鼠比较,白香丹组和巴氯芬组大鼠旷场得分显著降低(P<0.01,P<0.05),GBR1和GBR2蛋白在额区和下丘脑中的表达水平明显上升(P<0.01,P<0.05),但两组比较差异无统计学意义(P>0.05)。结论 GABABR亚基(GBR1和GBR2)表达的下调可能与PMS肝气逆证的发生密切相关;白香丹可对GBR1、GBR2的表达起到调节作用。

PMS肝气逆证诊断实验室参考指标的建立

目的:建立PMS肝气逆证实验室检测参考指标和判定参考值,揭示其部分微观机制。方法:全国7家单位联合进行流行病学调查,观察受试者和患者血清中微观指标变化,分别采用放射免疫法检测性激素和高效液相法检测单胺类神经递质。结果:肝气逆证组较正常对照组,E2、P在月经周期3个不同时期均有降低(P<0.05),PRL、5-HT、NE显著升高(P<0.01)。结论:PMS肝气逆证E2排卵期分泌峰低平与黄体期E2、P分泌峰阙如及PRL、5-HT、NE升高是PMS肝气逆证发病深层机制之一,E2、P、PRL、5-HT、NE是反映PMS肝气逆证诊断的实验室参考指标。

经前平颗粒对PMS肝气逆证模型大鼠顶区和额区皮质中μ阿片受体表达的影响

目的探讨PMS肝气逆证与μ阿片受体表达量的关系以及经前平颗粒的微观作用机制。方法以脉冲电刺激法制备PMS肝气逆证大鼠模型,运用半定量RT-PCR和Western blot技术检测PMS肝气逆证模型大鼠顶区和额区皮质中μ阿片受体的表达量。结果 PMS肝气逆证模型大鼠顶区和额区皮质中μ阿片受体的表达量均显著降低,给予经前平颗粒后能显著提高该基因表达。结论 PMS肝气逆证的发生可能与脑中枢顶区和额区皮质中μ阿片受体表达量下降有关,调节该基因表达异常可能是经前平颗粒的部分药理作用靶点。

舒郁胶囊对PMS肝气郁证模型大鼠海马μ阿片受体分布表达的影响

目的:探讨经前期综合征(PMS)肝气郁证模型大鼠海马脑区μ阿片受体(MOR)分布形态、蛋白水平表达,初步揭示PMS肝气郁证的发生机理及舒郁胶囊对该病证的干预作用。方法:采用慢性束缚应激法复制PMS肝气郁证模型大鼠,分别予以调肝方药舒郁胶囊进行干预。采用免疫荧光标记(IF)和蛋白免疫印迹(WB)技术对各组大鼠海马CA1、CA3脑区MOR进行检测。结果:与正常组大鼠相比,模型组大鼠海马脑区MOR分布排列杂乱且蛋白含量增多(P<0.01),给予药物干预后,MOR蛋白含量基本恢复至正常水平。结论:PMS肝气郁证的发病机理可能与大鼠海马中CA1、CA3区MOR高表达有关;舒郁胶囊可以有效纠正其恢复近正常水平,这可能是舒郁胶囊治疗PMS肝气郁证的中枢机制之一。

两种PMS肝气逆证大鼠模型造模方法的效果比对分析

目的:本文主要研究PMS肝气逆证标准化大鼠模型的造模方法。方法:分别采用情志刺激为主择时分段刺激造模法和情志刺激为主连续刺激造模法,制备PMS肝气逆证大鼠模型,选择氟西汀分散片和白香丹胶囊进行药物干预。通过对2种造模方法所得关键行为学指标结果进行比对分析,筛选出最佳造模条件。结果:①择时分段刺激造模法可以诱导大鼠的焦虑样行为,并且在非接受期减弱、接受期加强,大鼠的各行为学指标间发生明显的同步改变,给予临床PMS肝气逆证有效药物能够改善这一现象;与正常组相比,造模组的各项行为学指标具有统计学差异。②连续刺激造模法也可诱导大鼠的焦虑样行为,但给予药物干预后没有改善;在各项焦虑样行为指标中,仅进入开放臂时间百分比在接受期和非接受期存在明显变化;虽然与接受期相比,模型组大鼠非接受期进入开放臂次数和百分比下降、旷场实验总分提高,但其结果没有统计学差异。结论:情志刺激为主的择时分段刺激造模法,诱导出的PMS肝气逆证大鼠模型,更为契合PMS肝气逆证患者临床表现。

经前平对PMS肝气逆证大鼠海马β-内啡肽表达的影响

目的:通过观察中药对中枢神经递质受体表达的影响,探讨中药治疗情志障碍及经前期综合征(PMS)的微观机制。方法:脉冲电流结合噪音刺激大鼠,造成肝气逆PMS模型。分别给予生理盐水、经前平颗粒灌胃,连续4个月经周期,免疫组化法检测海马β-内啡肽阳性细胞。结果:处于发情期的PMS大鼠β-内啡肽(β-EP)阳性细胞表达显著低于同一月经周期的正常鼠(P<0.05),经前平颗粒能够缓解焦虑症状,且可以使大鼠海马β-内啡肽阳性细胞明显增多(P<0.05)。结论:中药经前平颗粒可能通过调节中枢β-内啡肽的表达,而治疗与PMS有关的情志障碍。

动态观测血清T_3、T_4、TSH在PMS肝气逆、肝气郁两证患者月经周期各时相的变化

目的:研究三碘甲状腺原氨酸(T3)、甲状腺素(T4)、血清促甲状腺素(TSH)在经前期综合征(PMS)肝气逆、肝气郁两证型中的变化规律。方法:采用流行病学横断面调查的方法,选取济南、青岛两市女性职工为目标人群,参照PMS国际诊断标准及证候诊断标准筛选患者。对PMS两证患者在经期的卵泡期(6-14天)、黄体期(15-23天)、经前期(24-28天)及月经期(1-5天)4个时期采集血样,放免法检测经期不同时段T3、T4、TSH水平。结果:与正常组比较,在经前期与经期,两证患者血清T3水平均显著降低(P<0.05);血清T4、TSH水平发病前较发病后改变不显著,但在发病前后的经期各个时相,均呈现显著性升高。结论:T3、T4、TSH的改变是肝气逆、肝气郁两证发病的机制之一。这一微观改变是机体"气血潜在不畅"的实质之—,是两证发病的机体条件。

白芍提取物对PMS肝气郁证大鼠下丘脑Cav1.2介导的CaM/CaMK Ⅱ/BDNF信号通路的影响

目的:本文主要探讨白芍提取物对PMS肝气郁证大鼠下丘脑Cav1.2钙通道关键蛋白CACNA1C及其下游信号通路中CaM、BDNF蛋白表达和对CaMKⅡ磷酸化的影响,从而明确白芍提取物治疗肝气郁结证的分子作用靶点。方法:利用慢性束缚应激法制备PMS肝气郁证大鼠模型,使用白芍提取物进行药物干预。模型制备成功后检测下丘脑CACNA1C蛋白表达,以及下游信号通路中CaM、BDNF蛋白表达和CaMKⅡ的磷酸化水平。离体培养海马原代神经元,通过KCl激活L型钙通道,检测白芍提取物中的有效成分单体芍药苷对细胞内钙超载的影响。结果:PMS肝气郁证大鼠下丘脑CACNA1C蛋白表达增加,CaMKⅡ磷酸化水平提高,BDNF表达减少,说明白芍提取物可显著改善上述蛋白表达异常的现象,抑制KCl激活的L型钙通道引起的细胞内钙离子浓度的增加。结论:白芍提取物可能是通过调控细胞内Cav1.2,抑制其下游CaM/CaMKⅡ信号通路的活化发挥治疗PMS肝气郁证的作用。

依据“患者自评表”制定PMS肝气逆证疗效评价参考标准的研究

目的:针对临床缺乏经前期综合征(PMS)肝气逆证疗效评价标准的情况,建立PMS肝气逆证疗效评价参考标准。方法:采用随机双盲对照多中心的原则,依据"PMS肝气逆证症状严重程度患者自评表"初步建立PMS肝气逆证疗效评价参考标准。结果:"经前平颗粒"和安慰剂对于PMS肝气逆证患者均具有治疗效果,经前平组疗效明显优于安慰剂组;"患者自评表"可以作为疗效评价指标。结论:初步建立PMS肝气逆证疗效评价参考标准,为PMS肝气逆证疗效评价行业标准的建立提供了参考。

深圳市福田区育龄女职工经前期综合征（PMS）的初步调查

目的了解深圳市福田区育龄女职工经前期综合征（PMS）的发生情况及影响因素。方法对深圳市福田区企事业单位21～49岁的育龄女职工860人进行问卷调查，了解PMS的发生情况以及可能的影响因素。结果问卷有效率为94．0％（808人），PMS的患病率为60．0％（485人），其中轻度占64．9％（315人），中度占30．3％（147人），重度占4．7％（23人）；PMS发生率较高的症状为精神症状如情绪不稳定、易激怒，其次为躯体症状如头痛、乳房胀痛、腹胀腹泻等，也有少数有行为改变症状。文化程度高者的PMS患病率高于文化程度低者（P〈0．05）。结论PMS是育龄妇女较常见的疾病，应引起医务工作者的关注，并应针对妇女生理特点采取综合性干预措施。