定坤丹联合来曲唑治疗肾虚证多囊卵巢综合征不孕症临床疗效观察

目的 观察定坤丹联合来曲唑治疗肾虚证多囊卵巢综合征（polycystic ovary syndrome, PCOS）不孕症临床疗效。方法 选取经预处理后的肾虚证PCOS不孕症患者60例,随机分为治疗组和对照组,每组30例。对照组单独服用来曲唑,治疗组在对照组基础上加服定坤丹,比较两组患者月经周期第5天、第10天和肌肉注射人绒毛膜促性腺激素（human chorionic gonadotropin,hCG）诱发排卵当日雌二醇水平、子宫内膜厚度以及排卵情况、妊娠情况和临床疗效。结果 两组月经周期第5天子宫内膜厚度差异无统计学意义（P＞0.05）;治疗组月经周期第10天、肌肉注射hCG诱发排卵当日雌二醇水平、子宫内膜厚度均高于对照组（P＜0.05）;治疗组排卵情况、妊娠情况以及临床疗效均优于对照组（P＜0.05）。结论 定坤丹联合来曲唑治疗肾虚证PCOS不孕症有显著优势。     

二甲双胍联合来曲唑治疗多囊卵巢综合征排卵障碍性不孕的临床疗效研究

目的分析二甲双胍联合来曲唑治疗多囊卵巢综合征(PCOS)排卵障碍性不孕的效果。方法 80例PCOS排卵障碍性不孕患者作为研究对象,按照随机数字表法分为对照组和观察组,各40例。对照组采用来曲唑治疗,观察组采用二甲双胍联合来曲唑治疗。比较两组患者治疗效果、不良反应发生情况及治疗前后黄体生成素(LH)、睾酮(T)及雌二醇(E2)水平。结果观察组治疗总有效率为95.00%,显著高于对照组的77.50%,差异有统计学意义(P<0.05)。治疗后,观察组LH(7.04±0.51)U/L、T(1.54±0.24)nmol/L及E2(134.53±1.56)pmol/L均低于对照组的(8.85±0.86)U/L、(2.72±0.33)nmol/L、(142.85±2.62)pmol/L,差异有统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义(P>0.05)。结论对PCOS排卵障碍性不孕患者采用二甲双胍联合来曲唑治疗,其治疗效果更佳。     

高剂量来曲唑在卵巢低反应患者微刺激方案中的临床观察#br#

Objective?To explore the clinical application value of high-dose letrozole in poor ovarian response(POR) patients during mild ovarian stimulation protocols receiving IVF/ICSI. Methods?A retrospective analysis was performed on 102 patients with POR treated with letrozole mild ovarian stimulation in IVF/ICSI at our reproductive Center from January 2016 to December 2018. The high-dose letrozole group (7.5 mg/d×5 d) was the high-dose group (n=50), and the conventional letrozole group (5 mg/d×5 d) was the conventional dose group (n=52). Results?The age and basal FSH of the high-dose group were higher than those of the conventional dose group (P<0.05), and the number of sinus follicles (AFC) in the high-dose group was significantly lower than that in the conventional dose group (P<0.05). The time of use of gonadotropin (Gn) in high dose group was shorter than that in conventional dose group (P<0.05), the daily serum E2 level of human chorionic gonadotropin (hCG) was significantly decreased (P<0.05), the egg number was lower than that in conventional dose group, but the egg MⅡrate was significantly higher than that in conventional dose group (P<0.05). The clinical pregnancy rate and live birth rate per fresh transplant cycle increased in the high-dose group [55.56% vs 50%; 55.56% vs 37.5%], but the difference was not statistically significant compared with the conventional dose group (P>0.05). Conclusion?For POR patients receiving ART, high-dose letrozole with mild ovarian stimulation protocol can improve the clinical pregnancy outcome of POR patients to some extent without obvious adverse reactions, especially for POR patients with poor ovarian reserve, which may benefit from improving oocyte quality and high MII rate suggesting improved follicle quality.     

来曲唑与克罗米芬对多囊卵巢综合征患者促排卵效果观察

目的:探讨来曲唑与克罗米芬治疗女性不孕多囊卵巢综合征(PCOS)的临床疗效。方法:选择我院2010年9月~2012年8月收治的50例诊断为PCOS的女性不孕症患者,随机分为来曲唑组和克罗米芬组各25例,并进行排卵期护理宣教。结果:来曲唑组患者共完成26个周期的治疗,克罗米芬组患者共完成25个周期的治疗。两组患者卵泡成熟天数、子宫内膜厚度、优势卵泡数、成熟卵泡数、妊娠率和卵泡发育率差异均无统计学意义(P0.05),但来曲唑组的排卵率显著高于克罗米芬组(P0.05)。来曲唑组患者未出现异位妊娠和卵巢过度刺激综合征,克罗米芬组有1例发生卵巢过度刺激综合征。结论:来曲唑在治疗PCOS引起的女性不孕症中,可显著提高患者的排卵率。     

Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer

OBJECTIVE: To explore the predictive value of estrogen-regulated gene changes as indicators of sensitivity in ovarian cancer patients treated with the aromatase inhibitor Letrozole. METHODS: Expression of a range of proteins was assessed by semi-quantitative immunohistochemistry in tissue sections from the tumors of patients treated with Letrozole. Expression was correlated with clinical response to Letrozole. Corresponding mRNA in ovarian cancer cell lines treated with 17beta-estradiol (E2) was measured by quantitative RT-PCR. RESULTS: In an estrogen receptor (ER)-positive ovarian cancer cell line, quantitative RT-PCR analysis demonstrated that PLAU, VIM, BIGH3, CDH6, FN1, CASP4, KRT4, KRT7, KRT13, TRAM and NGAL were down-regulated and TFF1, TFF3, TRAP1, TFAP4, MYC, CTSD, IL17BR, TOP2A, CCNB1, CCNB2, PDZK1 and UBE2C were up-regulated by E2. The E2 modulation of these genes was reversed by the anti-estrogen tamoxifen and was ERalpha-dependent. For ovarian cancer patients treated with Letrozole, we tested the predictive value of the majority of these genes in paraffin sections from their primary tumors by semi-quantitative immunohistochemistry. Significant differences in expression levels of TFF1, TFF3, BIGH3, TRAP1, VIM, TOP2A, PLAU and UBE2C were observed between tumors from CA125 responsive/stable patients as opposed to tumors from patients whose disease progressed, using serum levels of CA125 as an indicator of response. Aromatase expression in the ovarian cancers also differed between these 2 groups of patients. CONCLUSION: These results suggest that expression levels of certain proteins in ovarian cancers are estrogen-regulated and could help identify patients who would benefit from endocrine therapy.     

The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen in post-menopausal women with early stage breast cancer

BackgroundAromatase inhibitors (AIs) may increase cardiovascular risk relative to tamoxifen in post-menopausal women with breast cancer. This risk has not been well-quantified outside of clinical trials.MethodsObservational population-based cohort study of women aged >55 years diagnosed with stage I–III breast cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed to March 2012. The primary outcome was hospitalisation for myocardial infarction (MI). Cause-specific hazards were compared using tamoxifen as the reference group. Inverse probability of treatment weighting using the propensity score was used to reduce confounding due to measured baseline covariates. Results were confirmed using two cause-specific hazards models. Subgroup analyses included women aged ≥66 years, those with prior ischaemic heart disease, and a ‘lower-risk group’ aged <74 years with stage I–II cancer and no prior ischaemic heart disease.ResultsIn 7409 aromatase inhibitor-treated and 1941 tamoxifen-treated women, the median age was 71 versus 74 years, respectively (p < 0.001). Baseline prevalence of ischaemic heart disease was similar (17.0% versus 16.9%, p = 0.96). Over a mean of 1184 d of follow-up, there were 123 hospitalisations for MI; the cause-specific hazard was higher with AIs (hazard ratio 2.02; 95% confidence interval 1.16–3.53 in the weighted sample). We observed comparable patterns within pre-defined subgroups and when adjusted using cause-specific hazards models.ConclusionAromatase inhibitors are associated with a higher risk of MI compared with tamoxifen. This risk should be accounted for when managing aromatase inhibitor-treated women.     

不同方法治疗内分泌失调性不孕症患者的疗效分析

目的 探讨来曲唑与克罗米芬对内分泌失调性不孕症子宫内膜厚度的影响及疗效.方法 随机选取2011年3月至2014年10月本院收治的内分泌失调性不孕症患者80例,依据治疗方法将这些患者分为来曲唑组(n=40)和克罗米芬组(n=40).对两组患者的子宫内膜厚度及不良反应发生情况进行统计分析.结果 来曲唑组治疗第1～6个月的子宫内膜厚度显著大于克罗米芬组(P＜0.05),妊娠患者排卵前子宫内膜厚度显著大于克罗米芬组(P＜0.05),排卵前子宫内膜厚度≥10 mm的发生率为58.8％(10/17),显著高于克罗米芬组的26.3％(5/19)(P＜0.05),不良反应发生率为5.0％(2/40),显著低于克罗米芬组35.0％ (14/40) (P＜0.05).结论 来曲唑较克罗米芬在内分泌失调性不孕症患者临床治疗中的效果显著,患者的子宫内膜厚度较大,不良反应发生率较低,值得推广.     

红金消结胶囊联合来曲唑治疗子宫肌瘤的临床研究

目的探讨红金消结胶囊联合来曲唑片治疗子宫肌瘤的临床疗效。方法选取2016年1月—2017年1月在新乡市第一人民医院进行诊治的子宫肌瘤患者54例临床资料进行回顾性分析,根据用药差别将入组患者分为对照组和治疗组,每组各27例。对照组在月经结束后第1天口服来曲唑片,2.5 mg/次,1次/d。治疗组在对照组基础上口服红金消结胶囊,1.2 g/次,3次/d。两组均以1个月经周期为1个疗程,治疗3个疗程。观察两组的临床疗效,比较两组的子宫体积、子宫肌瘤体积、血清性激素和细胞因子水平。结果治疗后,对照组和治疗组的总有效率分别为77.78%、96.30%,两组比较差异有统计学意义(P0.05)。治疗后,两组子宫肌瘤体积和子宫体积均显著缩小,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显小于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清雌二醇(E_2)、孕酮(P)、促卵泡成熟激素(FSH)、黄体生成素(LH)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清血管生成素-2(Ang-2)、血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)、人附睾蛋白4(HE4)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论红金消结胶囊联合来曲唑片治疗子宫肌瘤具有较好的临床疗效,可缩小子宫肌瘤体积,改善E_2、P、LH、FSH、Ang-2、VEGF、MMP-2、HE4水平,具有一定的临床推广应用价值。     

国产与进口阿那曲唑片在健康人体生物等效性研究

目的：研究国产阿那曲唑片在人体内的生物利用度,并与参比制剂比较,评价两者生物等效性。方法20名健康男性志愿者随机口服国产阿那曲唑片（受试制剂）或进口阿那曲唑片（参比制剂）1 mg后,采用高效液相色谱串联质谱法测定不同时刻血浆中阿那曲唑的浓度,用WinNonlin 5.2.1数据统计软件计算药代动力学参数,并评价其生物等效性。结果单次口服国产阿那曲唑片1 mg或参比制剂1 mg后,受试制剂和参比制剂的Tmax分别为（1.45±0.5） h和（1.50±0.63） h,Cmax分别为（16.962±4.291） ng·mL-1和（15.928±3.799） ng·mL-1,T1/2分别为（40.00±7.27） h和（42.50±10.81） h,用梯形法计算,AUC0-t分别为（722.7±139.6） ng·h·mL-1和（730.3±138.6） ng·h·mL-1, AUC0-∞分别为（791.8±149.3） ng·h·mL-1和（807.5±156.6） ng·h·mL-1。经方差分析、双单侧t检验和[1-2α]%置信区间法进行生物等效性评价。结果表明,受试制剂与参比制剂间各药动学参数的差异无统计学意义（P〉0.05）。结论国产与进口阿那曲唑片在人体内具有生物等效性。     

国产来曲唑片应用于乳腺癌内分泌治疗的 生物等效性研究

目的：研究国产来曲唑片在人体内的生物利用度,并与参比制剂比较,评价其生物等效性。方法20名健康男性志愿者随机口服国产来曲唑片2.5 mg（受试制剂）或进口来曲唑片2.5 mg（参比制剂）后,采用高效液相色谱法测定不同时刻血浆中来曲唑的浓度,用WinNonlin5.2.1数据统计软件计算药代动力学参数,并评价其生物等效性。结果单次口服国产来曲唑片2.5 mg或参比制剂2.5 mg后,药代动力学参数分别为：受试制剂的t1/2：（43.91±12.68）h、Cmax：（30.94±7.05）ng·mL^-1、Tmax：（2.13±2.59）h、AUC0-t：（1478±421）ng·h·mL^-1;参比制剂的t1/2：（40.49±12.23）h、Cmax：（27.93±5.41）ng mL^-1、Tmax：（2.20±1.72）h、AUC0-t：1503±396 ng·h·mL^-1。经方差分析、双单侧t检验和[1-2α]％置信区间法进行生物等效性评价,其中Tmax采用非参数检验法,结果表明受试制剂与参比制剂间的各药动学参数的差异无统计学意义（P〉0.05）。结论国产来曲唑片与进口来曲唑片在人体内具有生物等效性。