Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors

The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor(PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea

Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods： This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol （E2） and follicle-stimulating hormone （FSH）,feeding, pregnancy, parity, abortions, and body mass index （BMI）. The odds ratio （OR） and 95% confidenceinterval （95% CI） of different risk factors were estimated.Results： A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 （65.42%） werepremenopausal patients and 621 （34.58%） were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age （OR： 1.856, 95% CI：1.732-1.990）, serum concentration of E2 （OR： 0.976, 95% CI： 0.972-0.980） and FSH （OR： 1.060, 95% CI：1.053-i.066）, and menarche age （OR： 1.074, 95% CI： 1.009-1.144） were found to be associated with the patients＇menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit （P）=-28.396＋0.536Age-0.014E2＋0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions： The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

CLINICAL OBSERVATION ON ACUPUNCTURE TREATMENT OF 47 CASES WITH SECONDARY AMENORRHEA

Cases of secondary amenorrhea were treated by acupuncture, and the rate ofrestoring menstruation is relatively high. The total effective rate was 77%. But the some diseasewhich may cause amenorrhea is difficult to treat, such as hypo-ovaria praecox, pituitary micro-adenoma. The acupuncture has clear curative effect during primary course treatment. The amenorrhea withlactorrhea syndrome by the high prolactin (PRL) in the serum is also able to be treated by usingacupuncture.

Study on Correlation between Neuropeptide and Functional Hypothalamic Amenorrhea

ve To explore the correlation between neuropeptide and functional hypothalam-ic amenorrhea(FHA)

Primary amenorrhea with transverse vaginal septum and scant hematocolpos: A case report

Background: A genital outflow tract obstruction is an uncommon cause of primary amenorrhea. If ovulation occurs, menstrual bleeding is prevented. Patients typically present with abdominal/pelvic pain due to hematocolpos. Absence of significant hematocolpos could indicate a secondary source of primary amenorrhea and be challenging to the clinical diagnosis. Case: 17 year-old patient with primary amenorrhea, appropriate Tanner staging secondary sex characteristics, and transverse vaginal septum presents with virtual absence of hematocolpos. After vaginal septum resection, the patient began menstruating, although only evidenced by two cycles of vaginal spotting. Conclusion: Significant hematocolpos is an expected sequella of distal outlet obstruction when collated with secondary sexual characteristics. Absence of such along with suboptimal return of menstruation reflects pathophysiology which may be attributed to a coexistent disorder of the hypothalamus or higher central nervous system function.

Resolution of Amenorrhea and Chronic Constipation in an Adult Patient with Idiopathic Scoliosis Wearing a Scoliosis Activity Suit for 6 Months: A Case Report

Objective: To report the symptomatic and radiographic changes in an adult scoliosis patient with a history of amenorrhea and chronic constipation. Clinical Features: Patient presented for treatment with an 8-year history of amenorrhea and chronic constipation. Radiographic study showed a right thoracic/left lumbar double major scoliosis. Intervention and Outcome: Patient was fitted for a scoliosis activity suit and given instructions for continued home use, building up to 3 - 4 hours total daily. After 6 months of use, her amenorrhea and chronic constipation had resolved, and both scoliosis Cobb angles also improved. Scores on before and after SRS-22r questionnaires, as well as a quadruple numerical pain rating scale, also improved. Conclusion: A patient wearing a scoliosis activity suit for 6 months reported symptomatic changes as well as radiographic, pain, and quality of life improvements. The results of this case cannot be generalized. More investigation into the association of scoliosis and other organic symptoms is warranted.

Chemotherapy Induced Amenorrhea in Women Treated with Chemotherapy for Breast Carcinoma in Yalgado Ouédraogo Teaching Hospital in Ouagadougou, Burkina Faso

Background: We conducted this study to identify factors associated with the onset and reversibility of chemotherapy-induced amenorrhea in Yalgado Ouédraogo Teaching Hospital of Ouagadougou. Methods: A historical cohort study was performed and covered the period from 1 January 2014 to 31 July 2015. No menopausal patients managed for a histologically confirmed breast carcinoma and having benefited from chemotherapy were included in the study. Logistic regression analysis was used to determine the factors associated with the occurrence of chemotherapy-induced amenorrhea as well as its reversibility. Results: Seventy patients were included. The mean age was 38.5 years. Thirteen patients were obese and 19 (40.4%) had their menarche after age of 15 years. Adjuvant chemotherapy was administered to 31 patients while 12 had received neoadjuvant chemotherapy. Sequential chemotherapy with an anthracycline and a taxanetherapeutic protocol was the most used. Forty-seven patients had a chemotherapy-induced amenorrhea. The risk of having a chemotherapy-induced amenorrhea increases by 25% for each additional year of age at diagnosis of cancer (p = 0.0001). Obesity and menarche after age 15 were found to be protective factors. After adjusting these variables together, age, obesity, and age at menarche were factors independently associated with the occurrence of the chemotherapy-induced amenorrhea. The reversibility was effective in 11 cases (37.9%) and especially concerned patients younger than 40 years (p = 0.03). Conclusion: Age is the primary risk factor. Reliable markers of ovarian function need to be developed to better select fertility conservation protocols.

Discussion on the treatment of amenorrhea by "Tihujiegai method"

"Tihujiegai method"(lifting a kettle and removing its lid figuratively refers to a method of lifting the'Lung Qi'(It refers to the functional activity of the lungs and also includes breathing gases.)to promote urination.),created by Zhu Danxi(1281-1358),who ranked among the era’s best doctors,is a metaphor for using"Xuanfei method"(A method of promoting the dispersing function of the lung)or"Tiqi method"(A method for treating Qi activity depression),which has been widely used later.The author consulted a large number of relevant essays and found that the"Tihujiegai method"of amenorrhea was also effective.This study mainly discusses the treatment of amenorrhea method theoretically,and opens up ideas for clinical application.

Cytogenetic and Clinical Analysis of 340 Chinese Patients with Primary Amenorrhea

Objective To analyze the relationship between karyotypes and clinic features of patients with primary amenorrhea.Methods G banding was done for 340 patients with primary amenorrhea to facilitate individual chromosome identification,and if specific staining for certain portions of the chromosome was necessary,C banding was used.The clinical data were recorded by physical examination and ultrasound scanning.Results Karyotype analysis of the 340 patients revealed that 180(52.94%) patients had normal female karyotypes and 160(47.06%) patients had abnormal karyotypes.The abnormal karyotypes included abnormal X chromosome(150 patients),mosaic X-Y chromosome(4 patients),abnormal autosome(5 patients),and X-autosome translocation(1 patient).The main clinical manifestations in patients with primary amenorrhea were primordial or absent uterus(95.9%),invisible secondary sex features(68.8%),little or absent ovary(62.6%),and short stature(30.0%).The incidence of short stature in patients with X chromosome aberration(46%,69/150) was significangly higher that in patients with 46,XX(9.44%,17/180) as well as 46,XY(6.67%,3/45;χ2=146.25,P=0.000).All primary amenorrhea patients with deletion or break-point at Xp11.1-11.4 were short statures.Conclusions One of the main reasons of primary amenorrhea is choromosome abnormality,especially heterosome abnormality.It implies the need to routinely screen chromosomal anomalies for such patients.There might be relationship between Xp11.1-11.4 integrity and height improvement.

Cytogenetic analysis of patients with amenorrhea

Objective: To analyse the cytogenetic examination results and investigate the effect of chromosome abnormalities on amenorrhea.Methods: The routine cytogenetic analysis was performed, including the chromosome G band analysis and karyotype analysis of the cultured peripheral blood lymphocytes from the patients with primary amenorrhea or secondary amenorrhea.Results: One hundred and thirty-seven cases were found with chromosome abnormalities in 234 patients with primary amenorrhea. The incidence of chromosome abnormality was 58.6%. In 309 with secondary amenorrhea, the incidence of chromosome abnormality was 13.6%.The reported abnormalities included the numerical and structural abnormalities of X chromosome, 46,XY, 45,X0/46,XY,and the structural abnormality of autosome.Conclusions: Chromosome abnormality is one of the main causes of amenorrhea. Karyotype analysis of chromosome is absolutely necessary for the diagnosis and treatment of patient with amenorrhea.

磁共振成像在子宫及下生殖道先天发育异常致原发性闭经中的应用价值

目的探讨磁共振成像(MRI)对子宫及下生殖道先天发育异常所致原发性闭经的诊断价值。方法选取2015年11月至2023年5月就诊于首都医科大学附属北京妇产医院因先天发育异常导致原发性闭经的患者41例,回顾性分析其临床表现和MRI影像,总结影像学表现特点。结果结合临床表现和MRI表现,最终诊断先天性子宫阴道缺如(MRKH)综合征27例,雄激素不敏感综合征2例,处女膜闭锁6例,宫颈闭锁2例,阴道下段闭锁4例。27例MRKH综合征患者表现为子宫缺如或始基子宫,伴阴道部分闭锁19例、全程闭锁8例;2例雄激素不敏感综合征患者表现为子宫及宫颈缺如,阴道下段可见,1例性腺位于双侧腹股沟区,1例位于盆腔内髂外血管内侧并伴发肿瘤;6例处女膜闭锁患者表现为子宫腔、宫颈管及阴道全程不同程度积血,1例伴输卵管积血;2例宫颈闭锁患者同时合并阴道闭锁、输卵管积血;4例阴道下段闭锁患者表现为闭锁段上方阴道、宫颈管及宫腔增宽积血。结论MRI可清楚显示子宫及下生殖道发育异常,明确导致原发性闭经的病变部位,为患者下一步诊治提供可靠参考信息。

4例46,XY性发育障碍患者遗传学分析

目的:探讨4例46,XY性发育障碍发生的分子机制。方法:收集患者临床病历资料,采集其肝素抗凝外周血进行淋巴细胞培养,染色体G显带技术制备并分析染色体核型,提取外周血DNA行SRY基因检测和测序,SRY基因检测结果阴性者外送标本行性发育相关基因靶向测序,生物信息学方法分析测序结果。结果:查体显示4例患者社会性别均为女性,而外周血淋巴细胞核型分析结果提示核型均为男性(46,XY),社会性别与生物学性别不一致;性别决定基因SRY均为阳性,测序结果提示病例1为SRY基因编码区第5位碱基缺失(c.del5A),病例2为SRY基因编码区第5位碱基发生错义突变(c.5A>T),病例3为SRY基因编码区第6位碱基缺失(c.del6A),病例4的SRY基因检测范围内未见突变位点,靶向测序结果提示雄激素受体基因(AR)编码区发生错义突变(c.2117 A>G);生物信息学软件Mutation taster提示c.del5A、c.del6A和c.2117 A>G等3种突变可能导致疾病发生,c.5A>T突变可能为人群多态现象;Raptor X蛋白质三维结构预测软件分析结果显示SRY基因c.5A>T突变对SRY蛋白的三维构象没有影响,而AR基因c.2117 A>G突变可导致AR蛋白的三维结构明显变化,并增加两个氢键;PolyPhen-2显示SRY基因c.5A>T和AR基因c.2117A>G突变为可能致病;ClinvAR软件分析结果提示4种突变均未见临床病例报道。结论:基因突变可能是导致患者性器官发育异常的原因,基因检测有助于明确诊断以及家庭再生育咨询。

Late Diagnosis of Turner Syndrome in Adulthood;a Case Study from the Endocrinology-Diabetology Nutrition Department of the National Hospital of Pikine Senegal

Introduction: Turner syndrome is a rare genetic disorder characterised by the presence of one X chromosome and the absence of part or all of an X or Y chromosome and patients may experience delayed puberty and infertility. Our study aimed to evaluate the diagnostic delay in our practice and analyze the impact of this diagnostic delay on the effectiveness of patient management. Patients and Methods: Turner syndrome patients were identified from the endocrinology-diabetology nutrition department Database We examined the records of patients in whom the karyotype analysis favoured Turner syndrome. Results: We have selected 5 patients’ records of female patients with Turner syndrome. The mean age was 25, ranging from 19 to 29 years. Primary amenorrhea and characteristic dysmorphic features were observed in all patients. One married patient, who sought consultation for infertility, expressed a desire for pregnancy. Short stature was identified in 3 patients. Primary hypothyroidism and hypertension were respectively found in 1 and 2 patients. Gonadal dysgenesis was noted in 100% of cases. Karyotype analysis revealed monosomy X in 2 patients and mosaic patterns in others. All patients received estrogen-progestin treatment. Antihypertensive therapy was initiated for 2 patients. One patient is on L-thyroxine. In the short term, treatment led to the onset of menstruation after the initial months. Evaluation of treatment efficacy on internal genital organs is yet to be performed. Due to uncertain benefits at this age, growth hormone therapy was not considered for our patients. We provided counseling on assisted reproductive options for couples desiring to conceive. In our study, all patients were placed on estrogen-progestin therapy, and the response appeared favorable. Conclusion: In our practice, the diagnosis of Turner syndrome occurs very late in adulthood, at an age when growth hormone treatment is nearly ineffective. Treatment typically revolves around estrogen-progestin therapy, along with managing other comorbidities such as hypertension and primary hypothyroidism.

特纳综合征合并系膜增生性肾小球肾炎1例

特纳综合征(turner syndrome,TS)又名先天性卵巢发育不全,是一种由性染色体X数量或结构异常引起的疾病,发病率约为1/2500[1],诊断金标准为外周血染色体核型分析。TS患者可表现为身材矮小、多数智力正常、性腺功能低下、肘外翻、颈蹼等特征性体征[2]。TS常合并心血管畸形、自身免疫性疾病、泌尿系统畸形等[3]。TS合并系膜增生性肾小球肾炎的病例未曾报道,故对中南大学湘雅三医院诊断的一例TS合并系膜增生性肾小球肾炎患者进行报道。

《闭经诊断与治疗指南(2023版)》解读

闭经是临床常见的症状。由于其病因多样,包含各种生殖系统结构性异常、全身系统性疾病和内分泌功能紊乱,诊疗较复杂。2023年中华医学会妇产科学分会妇科内分泌学组发布了《闭经诊断与治疗指南》,该指南针对病理性闭经的定义、分类、发病机制、诊断、鉴别诊断与治疗进行了更新和补充,为闭经的精准诊断和治疗管理提供了相关建议。本文通过对《闭经诊断与治疗指南(2023)版》进行详细解读,重点分析闭经的诊断流程和生育相关问题的处理办法,使该指南更具有临床实践的指导意义,有助于闭经的规范化诊疗。

中枢性闭经患者代谢性指标的相关关系研究

目的探讨中枢性闭经患者代谢性指标异常的发生率,代谢异常指标和高同型半胱氨酸血症(HHcy)、糖代谢异常的相关关系。方法回顾性分析2021年12月1日至2022年6月1日太原市妇幼保健院生殖内分泌科门诊中枢性闭经患者60例为研究对象,同期检查的健康妇女60名,年龄14~40岁。进行血压测量、人体成分分析,并测定甲状腺功能、同型半胱氨酸(Hcy)、尿酸、肝功能、肾功能、血脂以及糖耐量试验和胰岛素释放试验。比较分析60例中枢性闭经患者代谢性指标异常的发生率,同时代谢性指标与Hcy及糖代谢具有相关性。结果中枢性闭经组患者与健康对照组相比,HHcy(87%与57%)、糖代谢异常(93%与50%)、总胆固醇(30%与13%)、三酰甘油(37%与8%)及高密度脂蛋白胆固醇(40%与17%)异常的发生率明显升高,差异有统计学意义(P<0.05);在中枢性闭经与多种因素的相关关系分析中,表明中枢性闭经的危险因素为糖代谢异常的发生、HHcy及高三酰甘油血症。结论中枢性闭经患者是HHcy、糖代谢异常及高脂血症发生的高危人群,建议对于中枢性闭经的患者要常规行Hcy、糖代谢及血脂等代谢性指标的检查,对指导综合治疗有重要意义。

基于一气周流理论浅析逍遥散治疗闭经

黄元御一气周流理论以“中土为轴,四象为轮”为基本框架结构,将人体生理病理与“土枢四象”的周流运转联系起来,为中医临床诊治疾病提供一种新的思路。逍遥散源自《太平惠民和剂局方》,在妇科病闭经的临床治疗方面起到了很好的效果,其方药组成可通过升木达郁、培补土气来恢复“一气周流”,而改善闭经“木气郁陷、中土气虚”的病机,恢复月经来潮。

基于网络药理学和分子对接探讨川牛膝治疗继发性闭经的作用机制

目的:基于网络药理学和分子对接技术探讨川牛膝治疗继发性闭经(secondary amenorrhea, SA)的作用机制。方法:从中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)检索川牛膝的活性成分及作用靶点,从GeneCards数据库获取SA的疾病靶点,采用R软件得到两者的交集靶点。借助STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络,通过Cytoscape 3.8.2软件进行聚类分析和拓扑分析从而筛选核心靶点。应用R软件进行基因本体(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)富集分析(P<0.05)。最后,采用Autodock Vina软件进行分子对接验证。结果:川牛膝活性成分4个,即槲皮素、β-谷甾醇、甜菜素、红苋甾酮;川牛膝作用靶点178个,SA相关靶点1 366个,两者的交集靶点56个;基于Network Analyzer插件的拓扑分析筛选得到9个核心靶点,包括丝氨酸/苏氨酸蛋白激酶(serine/threorine protein kinase, AKT1)、丝裂原活化蛋白激酶1(mitogen activated protein kinase 1,MAPK1)、雌激素受体1(estrogen receptor 1,ESR1)等。GO功能分析主要涉及对类固醇激素的反应、活性氧代谢过程、上皮细胞增殖等;KEGG通路135条,主要包括HIF-1信号通路、内分泌抵抗、雌激素信号通路等。分子对接显示,活性成分(槲皮素、β-谷甾醇)与核心靶点(AKT1、MAPK1)具有较好的结合活性。结论:川牛膝治疗SA具有多成分、多靶点、多途径的特点,其可能通过槲皮素、β-谷甾醇等成分作用于AKT1、MAPK1、ESR1等靶点,调控雌激素信号通路、内分泌抵抗等通路。

从发病机制探讨多囊卵巢综合征所致闭经

基于肝脾肾三脏,从肝郁气滞,脾虚痰湿,肾虚精亏及冲任二脉剖析多囊卵巢综合征所致闭经病机;此外,从遗传、环境污染、精神压力、胰岛素抵抗等因素简述现代医学发病机制;以肝气郁滞,疏泄不及,横逆己土作为切入点,浅析脾虚及肾,肾虚血瘀的发展历程。此外,从五行生克制化方面阐明了肾在该病中的主导地位,从肝郁、脾虚、肾亏的中医理论探讨了多囊卵巢综合征致闭经发病过程和病变特点,确立了疏肝理气、健脾燥湿、补肾填精的主要治法,同时对兼有痰浊内生、瘀血阻络者,提出化痰降浊,通络化瘀的治法。

基于“一气周流”理论阐释节食后闭经的病机与证治

“以瘦为美”成为当下的主流审美,不正当的减肥方式层出不穷,致使节食后闭经的发病率逐年增加。针对这一现象,试图在对“一气周流”理论认识的基础上,阐释节食后闭经的病机与症治,从而更加有效的进行辨证论治,拓宽临床治疗思路。清代著名医家黄元御提出一气周流理论,认为中气左升右降是人体气机运转的基本形式,月经为中气周流的结果和体现。通过研究,得到以下主要结论:脾胃亏虚、转运乏源是本病发生的起点,肝木郁陷是病机的关键,肾虚水寒、脾虚湿困是发展的重要环节。治疗原则以固护脾胃为本;补肾阳助左升之轮;通行木气以调畅情志;审因论治,兼以行气活血。