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高雄激素血症女性生殖损失的风险标志物。

Risk markers of reproductive loss in women with hyperandrogenism.

作者信息

Semeniuk Ludmyla M, Likhachov Volodymyr K, Yuzvenko Tetyana Y, Dobrovolska Ludmyla М, Makarov Oleg G

机构信息

Ukrainian Scientific And Practical Center of Endocrine Surgery, Endocrine Transplantation of Organs and Tissues of The Ministry of Health of Ukraine, Kyiv, Ukraine.

Ukrainian Medical Stomatological Academy, Poltava, Ukraine.

出版信息

Wiad Lek. 2018;71(8):1550-1553.

PMID:30684339
Abstract

OBJECTIVE

Introduction: The frequency of the pathological course of pregnancy with hyperandrogenism ranges from 21 to 48%. With the predominance of androgens against the background of lowering the normal products of steroidogenesis, a pro-inflammatory immune imbalance is formed, which causes a premature termination of the development of pregnancy. Many studies indicate that hyperandrogenism is a factor in the development of obstetric pathology, including placental dysfunction. The severity of obstetric complications of pregnancy in women with hyperandrogenism depends on the duration of the disease and the quality of preparation for pregnancy. Establishing early markers of endocrine hyperandrogenic imbalance in the body of a future mother and conducting timely therapy is the key to the successful completion of pregnancy. The aim: the establishment of hormonal-immunological changes and morphological and receptive structure peculiarities of the endometrium correlations in women with PCOS at the pregnancy planning stage.

PATIENTS AND METHODS

Materials and methods: 139 women with PCOS were screened at the stage of pregnancy planning. Diagnosis of PCI was conducted in accordance with the International Recommendations of Endocrine Society 2013 and the Rotterdam criteria of 2003. Endometrial aspiration was studied for the study of T and B lymphocyte populations, cytokine levels and endometrial receptors. Hormonal parameters were determined using the radioimmunological method using Immunotech (Czech Republic) and Siena Ire Sorin (France) kits. Normal values of the studied hormones in accordance with the recommendations of the manufacturer. In order to study the populations of T and B lymphocytes and endometrial receptors the aspirate, obtained by endometrial biopsies, was used taken on the 5-7 and 21-24 days of the menstrual cycle. The cytokines levels (INF-y, TNF-a, Il-4, Il-6, Il-8, Il-10) were estimated in the endometrium with the help of the test system "Protein contour" on immunoenzymatic analyzer "Multyskan EX" (Germany). The assessment of estrogens receptors at stroma and glands and progesterone receptors at stroma and glands was performed by H -Score system, lymphocytes count was carried out by the light microscope at 400 x 3 fields-of-view expansion. Statistical material analysis was carried out on the personal computer using the standard software package with applied statistical analysis (Excel 2003 and Statistica v. 6.0). The assessment of variables connection was carried out by Pirson's coefficient correlations. The statistical significance of differences was performed by the use of nonparametric Mann -Whitney criteria, χ2 and Fisher criterium. The significance threshold of statistical value was considered p = 0.05.

RESULTS

Results: In women with hyperandrogenism, there was a significant increase (p <0.05) in the level of DHEA-S, a decrease in the level of E2 and progesterone in the early follicular phase compared with the control group and an increase in body weight by 37.5%. At histological examination of the endometrium on the 5-7th day of the menstrual cycle there was a lag proliferative changes of the endometrium, and in one third of women hyperplastic process against the background of reduced proliferative activity. At GA there was a marked violation of expression of receptors as estrogens and progesterone stroma in all stages of the menstrual cycle. In women with hyperandrogenism, changes in the immunological profile of endometriosis with the prevalence of Th-1 orientation of immunity have been detected.

CONCLUSION

Conclusions: In women with hyperandrogenism there is a close correlation between the biochemical form of the domination of androgens, ovulatory dysfunction, immunohistochemical and morphological structure of the endometrium. Revealed features of pro-inflammatory direction of cytokine immunity.

摘要

目的

引言:高雄激素血症妊娠的病理过程发生率为21%至48%。在类固醇生成正常产物水平降低的背景下雄激素占优势时,会形成促炎性免疫失衡,导致妊娠发育过早终止。许多研究表明,高雄激素血症是产科病理发展的一个因素,包括胎盘功能障碍。高雄激素血症女性妊娠产科并发症的严重程度取决于疾病持续时间和妊娠准备质量。确定未来母亲体内内分泌高雄激素失衡的早期标志物并及时进行治疗是妊娠成功完成的关键。目的:确定多囊卵巢综合征(PCOS)女性在妊娠计划阶段子宫内膜的激素 - 免疫变化以及形态和容受性结构特点。

患者与方法

材料与方法:在妊娠计划阶段对139例PCOS女性进行筛查。根据内分泌学会2013年国际推荐和2003年鹿特丹标准进行PCOS诊断。对子宫内膜抽吸物进行研究,以分析T和B淋巴细胞群体、细胞因子水平及子宫内膜受体。使用来自捷克共和国的Immunotech试剂盒和法国的Siena Ire Sorin试剂盒,通过放射免疫法测定激素参数。所研究激素的正常数值依据制造商的推荐。为研究T和B淋巴细胞群体及子宫内膜受体,在月经周期的第5 - 7天和第21 - 24天进行子宫内膜活检获取抽吸物。借助德国“Multyskan EX”免疫酶标分析仪上的“Protein contour”检测系统评估子宫内膜中的细胞因子水平(INF -γ、TNF -α、Il - 4、Il - 6、Il - 8、Il - 10)。采用H - Score系统评估基质和腺体中的雌激素受体以及基质和腺体中的孕激素受体,通过光学显微镜在400倍放大、3个视野下计数淋巴细胞。使用标准软件包(Excel 软件包2003和Statistica v. 6.0)在个人计算机上进行统计材料分析。通过皮尔逊系数相关性评估变量之间的联系。使用非参数曼 - 惠特尼检验标准以及χ²检验和费舍尔检验来确定差异的统计学意义。统计值的显著性阈值设定为p = 0.05。

结果

结果:与对照组相比,高雄激素血症女性中硫酸脱氢表雄酮(DHEA - S)水平显著升高(p <0.05),卵泡早期雌二醇(E2)和孕激素水平降低,体重增加37.5%。在月经周期第5 - 7天对子宫内膜进行组织学检查时,发现子宫内膜增殖变化滞后,三分之一的女性在增殖活性降低的背景下出现增生过程。在月经周期的各个阶段,高雄激素血症女性的基质中雌激素和孕激素受体表达均明显受损。在高雄激素血症女性中,已检测到子宫内膜免疫谱的变化,以Th - 1免疫方向为主。

结论

结论:高雄激素血症女性中雄激素占优势的生化形式、排卵功能障碍、子宫内膜的免疫组化和形态结构之间存在密切相关性。揭示了细胞因子免疫的促炎方向特征。

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