Effects of menopausal hormone therapy-based on the role of estrogens,progestogens,and their metabolites in proliferation of breast cancer cells

Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated.The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy,with an elevated risk of breast cancer.The evidence currently available from randomized trials and observational studies is based on data from different populations,drug formulations,and routes of administration.Even though the risks of MHT and breast cancer have received a great deal of attention,information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed.Furthermore,the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied.Therefore,this review aimed to describe the biological effects of estrogen,progesterone,and their metabolites on the proliferation of breast cancer cells,based on relevant basic research and clinical trials,to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.

Detection of Estrogen Responsive Breast Cancer Circulating Tumor Cells: Assay Development for Anti-Hormone Therapy Resistance

Recent clinical trials with histone deacetylase inhibitors (HDACi) have shown increased progression free survival by re-sensitizing resistant estrogen receptor positive (ER+) breast cancer cells to hormone suppressive therapies (HT). However, these trials lacked a sensitive, specific assay to identify and monitor HDACi/HT sensitive or resistant tumors. We tested detection of ER expression and histone acetylation of chromatin at the growth regulation by estrogen in breast cancer 1 (GREB1) gene, an estrogen-responsive gene involved in ER expression, in circulating tumor cell (CTC) as potential candidate assays for HDACi/HT sensitivity. ER+ and ER- CTC were detected and isolated from breast cancer patient peripheral blood by high speed fluorescence activated cell sorting (FACS) for use in mRNA analysis and anti-acetylated histone-mediated Chromatin Immunoprecipitation (ChIP). cDNA from mRNA and DNA extracted from the ChIP isolates were quantified by real-time PCR for GREB1. CTC isolates from patients who had an ER+ breast cancer primary contained both ER+ and ER- cells. More ER+ than ER- CTC was found in HT sensitive patients compared to HT resistant patients (p = 0.0559). GREB1 was found in acetylated histone chromatin from both ER+ and ER- CTC. The number of ER+ and ER- CTC found in peripheral blood appears to parallel patient outcomes as to their sensitivity to HT. Acetylated histone analysis can detect chromatin containing GREB1 in CTC, suggesting it may be useful as a more specific measure of HDACi effects on breast tumor cells. A larger, longitudinal data set following patients through HT/HDACi trials is needed to confirm these observations and their development for clinical use.

EVALUATION OF NEUROPROTECTIVE EFFECTS OF LONG-TERM LOW DOSE HORMONE REPLACEMENT THERAPY ON POSTMENOPAUSAL WO-MEN BRAIN HIPPOCAMPUS USING MAGNETIC RESONANCE SCANNER

To investigate the effects of long-term low dose hormone replacement therapy （HRT） on postmenopaosal women in homone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy （MRS） parameters. Methods A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [ estradiol （E2 ） 0. 5-1.0 mg and progesterone 0.5-2.0 mg, once a day ] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay （ELISA）. The gene types of apolipoprotein E （ApoE） were measured by polymerase chain reaction, and the subjects with susceptible genes （ ApoE ε3/ε4） of Alzheimer＇s disease （AD） were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging （MRI）, and results in two groups were analyzed by statistical method. Results Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher （P 〈0. 05） except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups The results of hippocampus MRI for the subjects with susceptible genes ApoE ε3/ε4 （HRT group 14 cases, control group 11 cases） showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group （0. 406 ± 0.028） was signiticantlyhigher than control gronp （0.369±0.031, P〈0.05）. Theresults of ^1H MRS for the subjects with susceptible genes ApoE ε3/ε4 （ HRT group 12 cases, control group 11 cases） showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group （ 1.54±0. 08 ） were significantly higher than control group （ 1.45±0. 13, P 〈 0. 05）. Conclusions For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE ε3/ε3 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.

HRT-FET周期中雌激素水平与妊娠期高血压发生的关系

目的:探讨替代方案冻胚移植(HRT-FET)周期中患者补充孕激素前的雌激素水平对妊娠期高血压疾病(HDP)发生的影响。方法:回顾分析2017年5月至2022年5月于山东大学生殖医学中心经HRT-FET获单胎活产的3506例患者的临床资料。根据E 2水平将患者分成3组:组1(E_(2)≤137pg/mL,≤25%,866例),组2(137pg/mL<E_(2)≤240pg/mL,25.01%~75%,1806例),组3(E_(2)>240pg/mL,>75%,834例)。比较3组患者的妊娠期并发症及新生儿结局。结果:组3患者的HDP发生率明显高于组1(aOR=0.653,95%CI为0.463~0.920,P=0.015)及组2(aOR=0.750,95%CI为0.566~0.994,P=0.045)。各组间妊娠期糖尿病、前置胎盘、产后出血等妊娠期并发症及早产、过期产、SGA(小于胎龄儿)、LGA(大于胎龄儿)等新生儿不良结局发生率无显著差异。结论:替代方案冻胚移植周期中转化内膜前的高雌激素水平是妊娠期高血压疾病发生的独立风险因素。

Effects of hormonal replacement therapy on lipoprotein metabolism inpostmenopausal women with hyperlipodemia

Objective: To assess the effects of hormone replacement therapy (HRT) on plasma lipid levels and hormone levels in postmenopausal women. Methods: A total of 108 Chinese postmenopausal women with hyperlipodemia (mean age (65.3±0.7) years) were randomly divided into 3 groups (group Ⅰ , Ⅱ and Ⅲ). Patients in group Ⅰ received exclusive estrogen therapy (Premarin), those in group Ⅱ received combined therapy with estrogen and progestrone (Livial), and those in group Ⅲ were treated with placebo. At the end of 3 and 6 months of the therapy, the serum sex hormone and lipid levels were determined and compared with the baseline levels. Results: After 6 months’ therapy, in group Ⅰ, a statistically significant (P < 0.01) decrease or increase vs the baseline was observed in serum lipid levels: the tatal cholesteror (TC) dropped by 12.8%, triglyceride (TG) by 17%, low-density lipoprotein cholesterol (LDL-ch) by 29%, and high-density lipoprotein cholesterol (HDL-ch) was elevated by 14.6%. In group Ⅱ, TC levels was decreased by 8.7%, TG by 15.6%, LDL-ch by 33% and HDL-ch by 28.3%. The serum estradiol (E2) levels in both group Ⅰ and Ⅱ was increased significantly (P < 0.01). Conclusion: Estrogen replacement therapy (ERT) benefits the lipoprotein metabolism in postmenopausal women with hyperlipodemia but when progestational is added to the ERT, the beneficial effect of estrogen on blood lipids was reduced.

Symptomatic changes in postmenopause with different methods of hormonal therapy

Objective: The diversity of opinions on the adverse effects of medications used to treat postmenopausal symptoms has prompted the use of various routes and mechanisms of action that need to be explored because bioavailability of the medications can vary. In order to select the appropriate route of administration for hormonal therapy (HT), it is necessary to determine baseline therapeutic efficacy. Design: We designed a prospective, randomized study consisting of four groups of postmenopausal wo-men: group 1 received oral conjugated estrogens, group 2 received a synthethic steroid, group 3 received estradiol nasally in spray form, and group 4 used transdermal estradiol in the form of patches. Criteria used to evaluate effectiveness was the Greene scale, which evaluate six components. These criteria were applied to each patient before hormonal intervention and then each month for 6 months. Luteinizing hormone (LH), follicle stimulating horone (FSH) and estradiol concentration were determined by chemiluminescence. Student’s t-test was used for intra-group comparisons before and after treatment. Results: There was a significant decrease in the vasomotor and sexual component (p < 0.05) with the use of four HT types. For depression, a difference was observed with synthetic steroids and oral estrogens. Upon analyzing the somatic component there was a decrease in symptoms with nasal and transdermal routes. Psychological changes were observed with the use of oral synthethic steroids and transdermal patches. Anxiety component demonstrated differences with nasal spray and oral estrogens, although all HT forms in this component showed a pattern of irregular changes. Conclusions: Changes in the response could be due each route of administration and medication used. Absorption variability may exist, which has repercussions in the control of symptoms and should be taken into consideration when selecting the appropriate route of administration for patients beginning HT.

Dialogue between estrogen receptor and E2F signaling pathways: The transcriptional coregulator RIP140 at the crossroads

Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.

Topical 5-aminolevulinic acid photodynamic therapy improved refractory acne conglobata and perifolliculitis capitis abscedens et suffodiens rather than hidradenitis suppurativa

Acne conglobata(AC),perifolliculitis capitis abscedens et suffodiens(PCAS)and hidradenitis suppurativa(HS)are uncommon refractory chronic,inflammatory,scarring diseases but cause serious damage to the quality of life.These three diseases are associated with follicular occlusion.Several studies indicated topical 5-aminolevulinic acid photodynamic therapy(ALA-PDT)improved follicular occlusion besides acne treatment.So we attempted to apply ALA-PDT to medicine resistant AC,PCAS and HS.Topical ALA-PDT was applied to 10 patients with AC,seven patients with PCAS and three patients with HS for more than three sessions.All the patients completed the dermatology life quality index(DLQI)questionnaire and were assessed for the efficacy at the baseline and on two weeks after each treatment.Adverse effects were recorded at each visit.The results showed 25.5%(5/20,two cases of AC and three cases of PCAS)of patients achieved excellent improvement after three sessions of PDT and another 60.0%(12/20,eight cases of AC and four cases of PCAS)of patients achieved good improvement.15.0%(3/20,three cases of HS)got poor response(<20%lesions clearance).Anotherfive cases(three cases of AC and two cases of PCAS)also achieved excellent response after 5–7 sessions of PDT.We also found that papular/nodular,cyst/abscess showed higher clearance rate than sinus/¯stula(88.5%,86.1%versus 11.1%).DLQI was reduced after three sessions of PDT in AC and PCAS patients rather than HS patients.5-ALA-PDT could improve refractory AC and PCAS but could not lead to improvement in late stage of HS.The e±cacy increased with more treatment sessions.

Protective effect of estrogen and progesterone replacement therapy on rat cardiovascular function

Objective To observe the change of the cardiova scular effect of estrogen replaceme nt therapy in rat after treated with p rogesterone.Method Thirty female rates were randomly di vided into three groups:group A:ova rietcomy;group B:ovariectomy with estrogen replacement therapy and group C:ovariectomy with estrogen and progesterone replacement therapy.The estrogen receptors(ER)in the artery of the rat were measured and the serum level of nitric oxide(NO),endothelin-1(ET-1),prostacyclin(PGF 1a )and thromboxane(TXB 2 )were detected 2months later.Results(1)There was no apparent difference in ER expression,serum NO and PGF 1a level between group C and group B;these index of group B and C were higher than those of group A;(2)there was no significant difference in blood viscosity,the congregate i ndex of red blood cell and platelet adhesiveness rate between group B and C;these index of group B and C were lower than those of group A.Conclusion Estrogen replacement therapy addin g progesterone makes no influence on arterial ER expression,hemorheolo gy index and regulation of estrogen t o cardiovascular cytokines generation.It suggested that estrogen combined with progesterone replacement t herapy could be a safe and effective method to prevent coronary heart dis ease.

坤泰胶囊与激素替代疗法治疗更年期综合征有效性和安全性比较的Meta分析

目的通过Meta分析比较坤泰胶囊与激素替代疗法治疗更年期综合征的有效性和安全性。方法计算机检索PubMed、EMbase、The Cochrane Library、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、中国博士学位论文全文数据库、中国优秀硕士学位论文全文数据库、维普数据库、万方数据库;手工检索相关资料。按照Cochrane系统评价的方法,逐一评价纳入研究的质量,提取有效数据,采用Revman 5.0.2软件进行Meta分析。结果共纳入了8个随机对照试验,包括675例患者。结果显示,坤泰胶囊组与雌激素治疗组比较,Kupperman症状评分变化值[MD=1.91,95%CI(-0.31,4.12)]与有效率[OR=1.37,95%CI(0.66,2.85)]相近(P>0.05);雌二醇(E2)水平变化值[MD=-12.8,95%CI(-22.85,-2.76)]与FSH水平变化值[MD=17.96,95%CI(3.03,32.88)]方面低于雌激素治疗组;坤泰胶囊组与雌激素治疗组比较,在总不良反应发生率[OR=0.41,95%CI(0.24,0.73)]、乳房胀痛发生率[OR=0.65,95%CI(0.42,1.00)]以及阴道出血发生率[OR合并=0.26,95%CI(0.17,0.40)]方面,均明显低于雌激素治疗组。结论现有有限证据表明,与雌激素治疗组比较,坤泰胶囊也能一定程度地改善更年期妇女的临床症状,在改善体内激素水平方面不及雌激素治疗组,但对减少总不良反应以及乳房胀痛、阴道出血发生率上存有一定优势。

IVF-ET后补充小剂量雌激素不改善妊娠率

目的:探讨体外受精-胚胎移植(IVF-ET)黄体支持中补充小剂量雌激素(E2)对妊娠率的影响。方法:①回顾性分析912个IVF-ET周期,根据黄体支持方案将其分为A组(511个周期),给予黄体酮80mg/d;B组(401个周期),给予黄体酮80mg/d+补佳乐2mg/d,比较组间妊娠率;②按照hCG日与ET日E2比值,分为<4.0组(291个周期)和≥4.0组(220个周期),比较二组妊娠率,了解E2下降程度与妊娠的关系;③另选择IVF超排卵妇女因某种因素未行移植(24个周期)和自然周期排卵妇女(32个周期)比较黄体中期E2水平,以了解超促排卵对黄体中期E2的影响。结果:黄体期补充与不补充E2组间种植率和妊娠率均无差异(P>0.05);E2下降程度不同的二组间种植率和妊娠率也无差异(P>0.05)。IVF超排妇女黄体中期E2水平明显高于自然周期妇女(P<0.01)。结论:取卵后E2水平下降不影响IVF结局,补充E2进行黄体支持不能改善IVF妊娠率。

促性腺激素释放激素激动剂联合反向添加疗法治疗术后中重度子宫内膜异位症的Meta分析

目的评价促性腺激素释放激素激动剂(GnRHa)联合反向添加疗法用于我国中重度子宫内膜异位症患者术后疗效。方法检索cochrane central Register of Controlled Trials(CENTRAL)、the cochrane Library、PubMed、Medline、EMBASE、SCI、中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊全文数据库、维普数据库、万方数据资源,检索时间截止2013年3月,国家限制为中国,并辅以手工检索,根据入选标准选出RCT文献7篇,对其进行文献质量评价。采用RevMan5.1软件进行meta分析。结果①反加疗法组较GnRHa组增加雌激素(E2)水平,P<0.01,降低卵泡刺激素(FSH)水平,P=0.006,两组差异均有统计学意义。反加组与GnRHa组间CA125水平、黄体生成素(LH)水平差异无统计学意义。②在缓解疼痛VAS评分上反加疗法组与GnRHa组差异无统计学意义。③在药物不良反应中绝经症状严重程度(Kupperman评分)上反加疗法组缓解了使用GnRHa造成的绝经症状,两组差异有统计学意义,P=0.001,在骨密度、骨钙素水平上,两组差异无统计学意义。结论保守手术后中重度子宫内膜异位症患者应用反加疗法,可以减少由GnRHa引起的低雌激素水平,但是未能对于骨密度水平和疼痛症状有显著地改善。

IVF-ET周期中黄体期雌激素水平变化与妊娠关系的临床研究

目的：探讨体外受精-胚胎移植（IVF—ET）周期中黄体期雌激素变化与临床妊娠的关系，从而分析黄体期补充雌激素的必要性。方法：92个超排卵IVF／gg细胞浆单精子注射（ICSI）-ET周期按妊娠结局分为妊娠组和未妊娠组，两组患者均在取卵后常规单纯注射黄体酮60mg，在卵泡成熟日，即人绒毛膜促性腺激素（hCG）日及取卵后第7、10、13天（d7、d10、d13）测定血清雌二醇（E：）水平。①比较妊娠组和未妊娠组hOG日、d7、d10、d13E2水平及d7、d10、d13E2水平与hOG日E2水平的比值[E2（dn）／E2（hCG日）]。②分别以E2（d7）／E2（hOG日）、E2（d10）／E2（hCG日）、E2（d13）／E2（hOG日）值的25％、50％和75％为界点将所有患者分为A组（〈25％）、B组（25％-50％）、c组（〉50％～75％）、D组（〉75％）组，比较各组妊娠率。结果：①仅取卵后d13E2水平及E2（d13）／E2（hOG日）值妊娠组与未妊娠组差异有统计学意义（Z=-6．229，P〈0．01；Z=-3．426，P〈O．01）；②以E2（dn）／E2（hOG日）值的分组比较，仅d13的4组差异有统计学意义（P〈0．05）。结论：在使用超排卵的IVF／ICSI—ET周期中，黄体期雌激素的变化并不影响临床妊娠率，因而可不补充雌激素。

雌激素替代疗法与女性阿尔茨海默病关系的Meta分析

目的探讨雌激素替代疗法与女性阿尔茨海默病发病风险之间的关系。方法计算机检索PubMed、Springer、CBM、CNKI和维普数据库,查找雌激素替代疗法与女性阿尔茨海默病相关性的病例对照研究,检索时间从建库到2012年12月。评价纳入文献的方法学质量后,采用RevMan 5.0软件对提取的数据进行分析。结果共纳入7项病例对照研究,病例组1392例,对照组2719例。Meta分析结果显示AD组中雌激素替代疗法者所占比例明显低于对照组,差异有统计学意义[OR=0.68,95%CI(0.50,0.90),P=0.01]。结论雌激素替代疗法对女性阿尔茨海默病存在影响,且为保护因素。

IVF-ET周期中雌激素浓度的变化与妊娠结局的关联性研究

目的评估在IVF-ET周期中自注射HCG日至卵裂期胚胎移植(ET)日连续6 d血雌二醇(E 2)浓度的变化与妊娠结局的关联性。方法回顾性分析自2017年1月至2020年1月在淄博市妇幼保健院生殖医学中心接受IVF-ET治疗的41例患者,分为妊娠组(n=20)和非妊娠组(n=21),比较组间自HCG日(d 0)起连续6 d检测血清E 2水平(d 0 E 2、d 1 E 2、d 2 E 2、d 3 E 2、d 4 E 2、d 5 E 2)的差异;根据取卵日(d 2)相对于HCG日的E 2比值(d 2 E 2/d 0 E 2)的四分位数(P25,P75)分为A组(<P25,n=10)、B组(P25~P75,n=21)和C组(>P75,n=10),并根据胚胎移植日(d 5)相对于HCG日E 2比值(d 5 E 2/d 0 E 2)的四分位数(P25,P75)分为D组(<P25,n=10)、E组(P25~P75,n=21)和F组(>P75,n=10),分析各组促排卵后各种指标的差异。结果妊娠组各时点血清E 2浓度均高于非妊娠组,但均无统计学差异(P>0.05)。在A、B、C三组中,B组的正常受精数(8.05±3.09)显著高于A组(5.20±2.94)和C组(5.60±3.10)(P<0.05),但三组间妊娠率无统计学差异(P>0.05)。在D、E、F三组中,E组的正常受精率(69.68%)显著高于D组(61.54%)和F组(54.13%),优胚率(25.27%)显著低于D组(46.81%)和F组(41.03%),差异均有统计学意义(P<0.05),但组间妊娠率无统计学差异(P>0.05)。结论妊娠组自HCG日至胚胎移植日血清E 2浓度均稍高于非妊娠组;取卵日或胚胎移植日相对于HCG日E 2比值的不同并不影响临床妊娠率。

卵巢切除后脑缺血再灌海马CA1区ET-3和GFAP的表达

目的 :探讨脑缺血再灌损伤中雌激素与ET 3,GFAP的相互关系。 方法 :采用雌性昆明小鼠卵巢切除结合脑缺血再灌的动物模型及免疫组织化学方法。动物分为 3组 :①缺血再灌组 (IR) ,双侧颈总动脉结扎 7min ,再灌 1,3,5 ,14d ;②卵巢切除 /缺血再灌组 (OVX/IR) ,在缺血再灌前 1周作卵巢切除术 ;③假手术对照组。 结果 :对照组海马CA1区可见少量ET 3和GFAP免疫阳性细胞散在分布 ,IR组和OVX/IR组各时间点阳性细胞数明显增多 (P <0 .0 1)。缺血再灌 1d时 ,OVX/IR组ET 3和GFAP阳性细胞数明显高于IR组 (P <0 .0 1) ;5d时 ,OVX/IR组和IR组ET 3和GFAP阳性细胞数达高峰 ,在时空变化上存在一致性。 结论 :雌激素可能在缺血再灌的早期参与对ET 3和GFAP的调控而起保护作用。

PCOS患者IVF-ET助孕结局及与血清E2、TPO-Ab、TG-Ab、AMH水平关系

目的:分析多囊卵巢综合征(PCOS)患者体外受精-胚胎移植(IVF-ET)助孕结局及与血清雌二醇(E2)、甲状腺过氧化物酶抗体(TPO-Ab)、甲状腺球蛋白抗体(TG-Ab)、抗苗勒管激素(AMH)水平关系。方法:回顾性收集本院行IVF-ET助孕PCOS患者360例,依据使用人绒毛膜促性腺激素(HCG)日血清E2水平分为高、中、低E2组,依据TPO-Ab与TG-Ab检测结果分为甲状腺自身抗体(ATA)阳性组与阴性组,依据血清AMH水平分为高、中、低组,比较各组助孕结局。结果:E2中水平组受精率(81.7%)及临床妊娠率(56.9%)均高于另外两组(P<0.05),而另外两组无差异(P>0.05);ATA阳性组受精率(72.5%)低于ATA阴性组(79.7%),早期流产率(39.5%)高于ATA阴性组(17.2%)(P<0.05);移植胚胎数与优质胚胎数,低AMH组(1.43±0.20枚、3.07±0.60枚)<中AMH组(1.86±0.24枚、4.25±0.71枚)<高AMH组(2.45±0.25枚、7.52±1.02枚)(P<0.05)。结论:PCOS患者IVF-ET时,合理控制血清E2水平可增加患者受精率与临床妊娠率,ATA阳性可增加早期流产风险,高水平AMH患者可获得更好的移植胚胎及优质胚胎,为妊娠结局提供更佳条件。

雌激素对去卵巢大鼠血清NO、NOS及ET-1水平的影响

观察雌二醇 (E2 )替代疗法对去卵巢大鼠血清一氧化氮 (NO)、一氧化氮合酶 (NOS)及内皮素 - 1(ET - 1)水平的影响。选择 2 1只SD雌性大鼠 ,体重 (2 0 0± 10 ) g ,随机分为假手术组 ,去卵巢组 ,去卵巢 +E2 治疗组。一个月后将大鼠处死 ,测血清NO、NOS及ET - 1的含量。结果表明同假手术组相比 ,去卵巢大鼠血清NO与NOS显著降低 ,ET - 1水平显著升高 ;去卵巢 +E2 治疗组大鼠血清NO与NOS显著升高 ,而ET - 1显著下降(P <0 .0 5 )。结果显示 :E2 能对血管内皮NO、NOS及ET - 1起调控作用 ,这可能是E2 对抗动脉粥样硬化的作用机制。

绝经后女性激素替代治疗与尿失禁关系的Meta分析

目的系统评价绝经后女性激素替代治疗与尿失禁的关系。方法全面检索Pub Med、EMBase、Cochrane Library、CNKI、万方电子期刊,检索时间均为建库至2015年8月,纳入激素替代治疗与尿失禁关系的随机对照试验,并进行文献质量评价和资料提取,提取研究对象的基本特征、试验设计细节、治疗方案、有效例数,对同质研究进行Meta分析。结果共纳入8项研究,6项为高质量研究,2项为低质量研究。Meta分析结果表明:绝经后健康女性使用激素替代治疗会导致尿失禁的发生率增加〔RR=1.48,95%CI(1.30,1.68),P<0.000 01〕;绝经后存在尿失禁的患者在使用激素替代治疗后尿失禁症状未见明显好转〔RR=0.98,95%CI(0.76,1.26),P=0.87〕。结论绝经后的健康女性使用激素替代治疗后尿失禁的发生率会显著增加,而存在尿失禁的绝经后女性在使用激素替代治疗后不会改善尿失禁症状。

促性腺激素释放激素激动剂联合激素反向添加治疗子宫内膜异位症的Meta分析

目的应用循证医学方法对促性腺激素释放激素激动剂(GnRH-a)联合激素反向添加治疗子宫内膜异位症的疗效及安全性进行评价。方法计算机检索Cochrane图书馆临床对照试验数据库、MEDLINE数据库、EMBase数据库、中国生物医学文献数据库、中国知网数据库、维普数据库及万方数据库并辅以手工检索,收集国内外GnRH-a联合激素反向添加治疗子宫内膜异位症的随机对照试验(RCTs)。对纳入的研究提取资料,根据Jadad量表评价其方法学质量,提取有效数据,用RevMan5.1软件进行Meta分析。结果共纳入符合标准的RCTs 11个,均为GnRH-a联合反向添加治疗与单独应用GnRH-a治疗的比较。Meta分析结果显示:(1)GnRH-a联合反向添加组腰椎骨质丢失量低于单用GnRH-a组(P<0.05);(2)GnRH-a联合反向添加组患者的雌二醇水平高于单用GnRH-a组(P<0.05),而卵泡刺激素水平低于单用GnRH-a组(P<0.05);(3)GnRH-a联合反向添加组盆腔痛症状缓解方面与单用GnRH-a组比较,差异无统计学意义(P>0.05);(4)GnRH-a联合反向添加组患者的失眠、潮热症状发生率均较单用GnRH-a的患者低(P<0.05);(5)GnRH-a联合反向添加组血清低密度脂蛋白、甘油三酯水平与单用GnRH-a组相比,差异无统计学意义(P>0.05)。结论GnRH-a联合激素反向添加治疗在保持其治疗效果的同时,能够改善机体低雌激素状态,减轻和缓解围绝经期相关症状及骨质丢失,短期内对血脂代谢变化影响不大。