【作者】 赵晓燕；

【导师】 贾国丛；

【作者基本信息】 郑州大学 ， 外科学， 2012， 硕士

【摘要】 乳腺癌已成为严重威胁女性生命健康最常见的恶性肿瘤之一。近年来其发病率呈上升趋势,但随着诊断和治疗水平的提高,生存期逐渐延长,病死率逐渐降低。辅助化学疗法改善早期乳腺癌的预后前景是相当引人注目,尤其是年轻乳腺癌患者。这种获益伴随着短期或长期的细胞毒副作用,在改善乳腺癌患者的预后中越来越重要。其中一个长期的毒副作用是导致绝经前年轻女性患者卵巢功能衰竭及不孕。化疗在使乳腺癌患者获益的同时,也损害了其卵巢,导致卵巢功能减退,引起不孕甚至诱发提前或永久性闭经。正常卵巢的血流供应随着月经周期的改变而变化,决定着每侧卵巢的功能状态。在排卵前期,卵巢间质内血流较卵泡期更丰富,较多的血管通常围绕着优势卵泡,收缩期和舒张期的流速均升高,而后者升高更明显,形成低阻力型血流频谱。化疗引起卵巢早衰的乳腺癌患者雌激素水平下降,血管舒缩功能失调且卵巢间质部血管网的生成减少,引起间质部纤维增生,血管变的纤细且管壁顺应性下降,峰值流速减低,血管阻力增高及有效灌注不足,导致皮质变薄,皮髓质比例失调,皮质回声增强,卵巢萎缩,从而损害了患者的卵巢储备能力。卵巢储备是指卵巢皮质区卵泡生长及发育形成可受精的卵母细胞的能力,生殖潜能随着卵巢储备功能的下降而下降。戈舍瑞林是一种促黄体生成素释放激素类似物,长期使用可以抑制脑垂体促黄体生成素的合成,从而作用于卵巢,使血清中雌激素水平下降,并维持在绝经后水平。避免卵巢受化疗药物的作用,达到保护卵巢的目的。目的本研究通过对绝经前乳腺癌患者在常规化疗的同时给予戈舍瑞林治疗,以评估该制品对卵巢功能的保护作用。方法将2年内收治的80例绝经前乳腺癌患者临床资料,随机分成治疗组(常规化疗+戈舍瑞林组)和对照组(常规化疗组),每组40例。化疗期间和化疗后,分别测定两组患者血清中雌二醇(E2)、卵泡刺激素(FSH)的水平,并用彩超检测同时期两组患者的子宫和卵巢的大小、卵巢窦卵泡数(antral follicle count,AFC)、双侧卵巢髓质内间质动脉的血流频谱,观察两组患者月经情况及化疗期间与化疗结束后随访的1年内的激素水平的变化,并观察两组患者的子宫卵巢大小及形态,记录AFC、卵巢间质血流峰值流速(stromal peak sysolic veocityPSV)和阻力指数(resistance index RI)。数据分析采用SPSS17.0统计学软件处理。以P<0.05为差异有统计学意义,采用χ2检验。结果80例患者均完成化疗,化疗期间均引起月经周期紊乱。治疗组和对照组月经恢复人数比率分别为85%和55%,差异有统计学意义(P=0.007)。治疗组在戈舍瑞林及化疗联合治疗期间,E2水平减低到绝经后水平,FSH和LH也明显降低；对照组在化疗期间E2水平逐渐降低,FSH和LH则明显增加。治疗组子宫大小、卵巢体积、AFC、卵巢间质动脉峰值流速均小于对照组,而RI高于对照组；对照组PSV与E2呈正相关,与FSH呈负相关。治疗结束后随访的1年内,治疗组的子宫大小、卵巢体积、AFC、卵巢间质动脉峰值流速逐渐恢复正常。对照组的无明显变化。结论化疗前及化疗过程中应用戈舍瑞林,能有效地保护卵巢功能,使大多数中青年患者能维持正常月经及生育能力。更多还原

【Abstract】 Breast cancer is one of the most common malignancy in women. Raise the level of diagnosis and treatment of early breast cancer diagnosis rate has gradually improved, its fatality rate decreased survival time gradually extended. Adjuvant chemotherapy has significantly improved the outlook in early breast cancer (EBC), particularly in younger women. This benefit has however been accompanied by short-term and long-term toxicities which become increasingly important as prognosis improves. One of these long-term side effects is failure of ovarian function with associated infertility in young pre-menopausal women.However, breast cancer patients benefit from chemotherapy in the same time increasingly important as prognosis improves. Which also undermines their ovarian function induced ovarian dysfunction and lead to premature amenorrhea and infertility.Normal ovarian blood supply depends largely on the functional status of each side of the ovary varies with the menstrual cycle. Preovulatory ovarian stromal blood flow than the follicular phase of a richer, more blood vessels are usually around the dominant follicle, systolic and diastolic flow velocity increased, while the latter increased more significantly, the formation of low-resistance-type blood spectrum. Chemotherapy-induced premature ovarian failure patients, E2levels decreased, reduced vasomotor dysfunction and ovarian stromal, vascular network formation, causing the fibrous hyperplasia of the interstitial portion of the blood vessels become thin and wall compliance decreased, the peak velocity to reduce increased vascular resistance and effective hypoperfusion, resulting in thinning of the cortex,the imbalance of the cortex and medulla, cortex echogenic, ovarian atrophy, to the detriment of the patient’s ovarian reserve capacity.Ovarian reserve refers to the follicular growth and development of ovarian cortex to form the ability of the fertilized oocytes,reproductive potential decreased with the decline in ovarian reserve.Goserelin is generate a luteinizing hormone releasing hormone analogues, long-term use can suppress the pituitary luteinizing hormone synthesis, so that the serum estrogen levels decline, and remained in post-menopausal levels.ObjectiveTo assess the protective effect of goserelin on the ovarian function of the patients during chemotherapy for breast cancer.MethodsThe clinical data of the premenopausal patients with breast cancer over during a two-year period were retrospectively analyzed. The patients were divided into the study group (treated with Goserelin+conventional chemotherapy) and the control group (treated with conventional chemotherapy) with40cases.The menstrual status and the hormone levels during chemotherapy and first year follow-up after chemotherapy between the two groups were observed.Uterus and ovary size, antral follicle count, ovarian stromal blood flow were measured by color Doppler at the same time.ResultsAll the80patients finished their chemotherapy treatment and all of them developed menstrual disorders.The menstrual recovery rate of the observation group and the control group were85%and55%,respectively, and the difference between the two groups had statistical significance (P=0.007).Of the observation group, the serum oestradiol (E2)decreased to postmenopausal levels, and the serum levels of luteinising hormone(LH) and follicle stimulating hormone (FSH) were also significantly decreased during combination treatment (goserelin plus conventional chemotherapy).Of the control group, E2levels decreased gradually while FSH and LH level increased significantly during chemotherapy. Of the observation group, the size of the uterus, ovarian volume, AFC,ovarian stromal artery peak velocity less than the control group, while the RI higher than the control;Of the control group, PSV and E2was positively correlated with FSH was negatively correlated.One year follow-up after the end of treatment, the treatment group the size of the uterus, ovarian volume, AFC, ovarian stromal artery peak velocity gradually returned to normal.No significant changes in the control group.ConclusionGoserelin administered during chemotherapy can effectively prevent the ovarian function injury caused by chemotherapy, and can help maintain normal menstruation and fertility for those young and middle-aged patients.更多还原