米非司酮对人蜕膜雌,孕激素受体及血清生殖激素的影响

目的：了解米非司酮对人蜕膜雌激素受体（ＥＲ）、孕激素受体（ＰＲ）和生殖激素的影响。探讨米非司酮的抗早孕机理。方法：应用葡聚糖活性碳吸附（ＤＣＣ）法和酶联组化法测定正常和服米非司酮１００ｍｇ后的人蜕膜组织ＥＲ、ＰＲ；采用放射免疫法检测血清β－ｈＣＧ、雌二醇（Ｅ２）、睾酮（Ｔ）和孕酮（Ｐ）的水平。结果：口服米非司酮１００ｍｇ后，人蜕膜组织胞浆ＰＲ明显减少（Ｐ〈０．０５），而胞浆ＥＲ明显增多（Ｐ〈０．０     

子宫肌瘤与肌肉组织雌孕激素受体含量与月经周期及子 …

应用放射受体分析法测定４０例子宫肌瘤患者子宫肌瘤、肌肉组织雌激素受体（ＥＲ）、孕激素受体（ＰＲ）的含量，月经周期根据月经史经子宫内膜组织相来判断，比较两种组织ＥＲ、ＰＲ含量与月经周期及子宫内膜组织相的关系。结果：子宫肌瘤组织的ＥＲ、ＰＲ含量高于同一子宫正常肌层的含量（Ｐ〈０．０５）；子宫肌瘤与肌肉两种组织中ＥＲ含量在子宫内膜增殖期高于分泌期（Ｐ〈０．０２５，Ｐ〈０．０５），ＰＲ含量分泌期高于增殖期     

子宫肌瘤组织雌、孕激素受体及细胞增殖相关抗原与激素及细胞核体关系的探讨

应用ＡＢＣ法和计算机图象分析系统（ＩＡＳ），定量分析３９例子宫肌瘤患者子宫组织雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、细胞增殖相关抗原（Ｋ１ｉ－６７）的含量；对其中２２例应用放射免疫法测定血浆雌二醇（Ｅ＿２）、孕酮（Ｐ）、促黄体素（ＬＨ）、促卵泡素（ＦＳＨ）含量；以及对其中８例应用立体学方法进行细胞核体定量分析。结果：子宫肌瘤组的ＥＲ、ＰＲ、Ｋｉ－６７显著高于同一子宫正常肌层的含量（Ｐ＜０．０１）；子宫肌瘤的细胞核体数密度和体密度也显著高于同一子宫正常肌层的对应值（Ｐ＜０．０５，Ｐ＜０．０１）；子宫肌瘤的ＥＲ、ＰＲ与血浆的Ｅ＿２、Ｐ含量无明显相关性，而与ＬＨ、ＦＳＨ含量呈负相关（Ｐ＜０．０５）；Ｋｉ－６７与Ｐ呈正相关（Ｐ＜０．０５）；子宫肌瘤的ＥＲ与其细胞核体数密度呈正相关（Ｐ＜０．０５）。提示：子宫肌瘤的发生、发展与雌、孕激素、ＬＨ、ＦＳＨ及其受体含量有关，孕激素在肿瘤发生、发展中可能起协同作用。     

子宫颈癌和正常宫颈组织雌,孕激素受体的研究

采用单克隆酶联免疫测定法，检测了２１例宫颈癌（宫颈癌组）和１７例正常宫颈肌层纤维组织（正常组）的雌、孕激素受体水平。结果：正常组雌激素受体（ＥＲ）的阳性率为８８．２％，孕激素受体（ＰＲ）的阳性率为７４．５％，ＥＲ和ＰＲ均阳性者占７４．５％。宫颈癌组ＥＲ阳性率为６６．７％，ＰＲ阳性率为４２．９％，ＥＲ和ＰＲ均阳性者占３８．１％。两组ＥＲ状态和水平比较，差异无显著意义（Ｐ＞０．０５），但宫颈癌组的Ｐｋ阳性率和ＰＲ水平均明显低于正常组（Ｐ＜０．０５）。宫颈癌组织的ＥＲ和ＰＲ水平与肿瘤分期，组织学分级之间，差异无显著意义（Ｐ＞０．０５）。绝经前宫颈癌组织ＰＲ水平较绝经后明显升高。宫颈腺癌组织ＥＲ和ＰＲ水平均明显高于宫颈鳞癌。宫颈癌患者按血清雌二醇水平高低分组，ＰＲ水平和ＰＲ／ＥＲ比值比较，差异均有显著意义。     

重复性早期自然流产病人非孕期血清激素水平和子宫内膜组织ER、PR含量变化的研究

用放免法测定了４０例拟诊为由内分泌病因所致的重复性早期自然流产病人卵泡期和黄体期的血清雌二醇（Ｅ２）、孕酮（Ｐ）、卵泡刺激素（ＦＳＨ）、促黄体生成素（ＬＨ）和血清催乳素（ＰＲＬ）水平，同时用生化法测定了相应增生期和分泌期子宫内膜组织中胞浆及胞核的雌、孕激素受体含量。通过和对照组比较，发现重复性早期自然流产病人黄体期和卵泡期的Ｅ２水平均显著低于对照组（Ｐ＜０．００５和Ｐ＜０．０５），其余各项激素水平与对照组无差异（Ｐ＞０．０５）；其子宫内膜增生期的胞浆雌激素受体（ＥＲｃ）含量显著低于对照组（Ｐ＜０．００５），分泌期子宫内膜的胞浆孕激素受体（ＰＲｃ）含量亦明显低于对照组（Ｐ＜０．０５）；各期子宫内膜组织的胞核雌、孕激素受体含量在两组间无差异。表明卵巢雌激素分泌不足和子宫内膜组织的受体含量减低是导致该组病人反复自然流产的原因。     

过期妊娠孕妇机体过氧化与胎盘功能关系的研究

测定足月妊娠及过期妊娠红细胞超氧化物歧化酶（ＳＯＤ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活力，血清脂质过氧化物（ＬＰＯ）及血清Ｅ３，ｈＰＬ及血浆ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α（６ＫＰ）水平。结果显示过期妊娠者ＳＯＤ，ＧＳＨ－Ｐｘ活力明显低于正常足月妊娠，Ｐ〈０．００１，ＬＰＯ明显高于正常足月妊娠，Ｐ〈０．０５，同时Ｅ３，ｈＰＬ下降，Ｐ〈０．００１，６ＫＰ亦降低，Ｐ〈０．０５。在过期妊娠期中     

稳定期系统性红斑狼疮孕妇外周血淋巴细胞亚群及白细胞介素-2受体的变化

目的：探讨系统性红斑狼疮（ＳＬＥ）孕妇在ＳＬＥ稳定期外周血中的Ｔ淋巴细胞亚群、自然杀伤细胞（ＮＫ细胞）及可溶性血清白细胞介素－２受体（ＳＩＬ－２Ｒ）的改变。方法：采用流式细胞仪对１４例ＳＬＥ稳定期（仅服用小剂量激素）的患者妊娠时（ＳＬＥ＋ＮＰ组）的Ｔ细胞亚群和ＮＫ细胞进行检测，同时用固相酶联反应法（ＥＬＩＳＡ）检测其ＳＩＬ－２Ｒ。并以１８例稳定期ＳＬＥ未孕妇女（ＳＬＥ组）、２０例正常未孕妇女（ＮＮＰ组）和２０例正常孕妇（ＮＰ组）作对照。结果：ＳＬＥ＋ＮＰ组的辅助性－诱导性Ｔ细胞（ＣＤ４＋）细胞数量较其他３组有明显下降（Ｐ＜０．０１）；ＣＤ４＋／细胞毒性－抑制性Ｔ细胞（ＣＤ８＋）值，ＳＬＥ＋ＮＰ组较ＳＬＥ组和ＮＮＰ组有显著下降（Ｐ＜０．０１），ＮＰ组也有下降，ＳＬＥ＋ＮＰ组和ＮＰ组之间差异无显著性（Ｐ＞０．０５）。ＮＫ细胞数在４组间差异无显著性（Ｐ＞０．０５）；ＳＬＥ＋ＮＰ组ＳＩＬ－２Ｒ有明显增高（Ｐ＜０．０１），其他３组变化不显著（Ｐ＞０．０５）。结论：ＳＩＬ－２Ｒ和ＣＤ４＋细胞数量变化可能对判断稳定期ＳＬＥ孕妇病情进展有重要作用     

子宫肌瘤与肌肉组织雌孕激素受体含量与月经周期及子宫内膜组织相关系的探讨

应用放射受体分析法测定４０例子宫肌瘤患者子宫肌瘤、肌肉组织雌激素受体（ＥＲ）、孕激素受体（ＰＲ）的含量，月经周期根据月经史及子宫内膜组织相来判断，比较两种组织ＥＲ、ＰＲ含量与月经周期及子宫内膜组织相的关系。结果：子宫肌瘤组织的ＥＲ、ＰＲ含量高于同一子宫正常肌层的含量（Ｐ＜０．０５）；子宫肌瘤与肌肉两种组织中ＥＲ含量在子宫内膜增殖期高于分泌期（Ｐ＜０．０２５，Ｐ＜０．０５），ＰＲ含量分泌期高于增殖期（Ｐ＜０．０２５）。２３例有正常月经周期者，１５例与子宫内膜组织相符合，８例与子宫内膜组织相不符合。１５例无正常月经周期者，子宫内膜组织相多为增殖期改变，占８０％。提示：子宫肌瘤的发生、发展与雌、孕激素及其受体含量有关，孕激素在肿瘤发生、发展中可能起协同作用，提示抗孕激素治疗子宫肌瘤的可能性。     

子宫内膜异位症患者内膜雌,孕激素受体测定及口服棉酚后的变化

采用葡聚糖活性碳吸附法，对２７例正常生育妇女（对照组）及２４例子宫内膜异位症患者（Ｅｍ组），测定了宫腔内膜雌激素胞浆受体（ＥＲｃ）、孕激素胞浆受体（ＰＲｃ）浓度。并测定Ｅｍ组中１５例口服醋酸棉酚２个月后，月经周期同日测定ＥＲｃ及ＰＲｃ浓度；同时对１６例手术切除的子宫、附件标本的原位内膜与异位内膜的ＥＲｃ、ＰＲｃ浓度进行比较。结果：对照组子宫内膜ＥＲｃ、ＰＲｃ浓度呈周期性变化，以卵泡晚期最高，黄体中期显著下降（Ｐ＜０．０５），黄体晚期进一步降低。Ｅｍ组原位内膜ＥＲｃ、ＰＲｃ浓度及周期性波动与对照组无差异，但异位内膜ＥＲｃ、ＰＲｃ浓度显著低于原位内膜（Ｐ各＝０．００３６及＜０．０００１），且失去周期性变化。口服棉酚２个月后血清雌二醇、孕酮浓度无显著下降，４例（２６．７％）患者子宫内膜组织相显示腺体分泌减少，但原位内膜ＥＲｃ、ＰＲｃ浓度却已显著降低（Ｐ＝０．０２１７及０．０１）。本研究提示：异位内膜与原位内膜对内源性性激素反应的不同步现象与异位内膜雌、孕激素受体浓度低下有关；棉酚对原位内膜ＥＲｃ、ＰＲｃ浓度的早期抑制现象，并不依赖于对卵巢功能的抑制作用，这一作用途径应对异位内膜同样有效。     

促黄体激素释放激素激动剂的临床应用及对骨代谢的影响

应用促黄体激素释放激素激动剂（ＬＨＲＨ－Ａ）２００μｇ，每日肌内注射，连续３个月为１疗程，治疗轻、中型子宫内膜异位症、子宫肌瘤、子宫腺肌症共２０例。结果：用药结束时，促卵泡成熟激素（ＦＳＨ）、黄体生成素（ＬＨ）、雌二醇（Ｅ＿２）均受抑制，分别为４．８±２．９ＩＵ／Ｌ（Ｐ＞０．０５）、４．０±３．５ＩＵ／（Ｐ＜０．０５）、１６０．３±１１０．７ｐｍｏｌ／Ｌ（Ｐ＜０．００１）。临床上体征改善，痛经消失，副反应轻，易为病人接受。２０例用药前后骨钙素（ｏｓｔｅｏｃａｌｃｉｎ）与尿钙、磷测定比较，差异均无显著性（Ｐ＞０．０５）。双能Ｘ线吸收法（ＤＥＸＡ）测量腰椎２～４骨密度，用药３个月下降２％，停药３个月下降１％，尚属正常范围（Ｐ＞０．０５）；单光子吸收法（ＳＰＡ）测量桡、尺骨骨密度也未见影响（Ｐ＞０．０５）。     

己酸孕酮、三苯氧胺及氨基导眠能对子宫内膜癌作用的研究

将子宫内膜癌７４例，分为７组单独或联合应用己酸孕酮，三苯氧胺和氨基导眠能治疗，光镜观察用药前后子宫内膜癌的形态学改变。结果：上述药物均能不同程度地抑制癌细胞生长，促其向成熟转化或发生退变，其中以三苯氧胺的作用尤为明显。癌细胞对上述药物的反应程度与癌分型、核分级有关，腺鳞癌、透明细胞癌和浆液乳头型腺癌反应不明显，而内膜型腺癌反应明显，两者的反应率有高度显著性差异（Ｘ２＝２０．８６Ｐ＜０．０１），粘液型腺癌反应介于两者之间。癌对药物反应程度随核分级增加而下降。     

己酸孕酮治疗子宫内膜癌前期病变的生殖激素水平变化

孕激素类药物治疗子宫内膜癌已有３０多年历史，具有一定疗效，但孕激素类药物的作用环节尚不明确。本研究用己酸孕酮治疗１４例子宫内膜癌前期病变患者，观察用药前后生殖激素水平的变化。结果表明，促黄体生成激素（ＬＨ）、促卵泡激素（ＦＳＨ）与促黄体生成激素比值（ＬＨ／ＦＳＨ），均比用药前明显下降（Ｐ＜０．０５，Ｐ＜０．０１）。提示：孕激素类药物的作用是多环节的，其中作用于垂体部位，选择性的影响ＬＨ分泌和ＬＨ／ＦＳＨ是环节之一。     

Can primary endometrial carcinoma stage I be cured without surgery and radiation therapy?

The data on 19 cases of primary endometrial carcinoma, stage I (mean age 28.0 years), cured by the administration of hydroxyprogesterone caproate without surgery and radiation therapy are presented. Clinical recovery in 15 cases was confirmed by repeated cytological and histological examinations of the endometrium. Hydroxyprogesterone caproate dose per course ranged within 25.0-83.0 g. In 4 patients with moderately differentiated cancer (G2), hormonal treatment was carried out in combination with chemotherapy. When tumor regression was confirmed histologically, steroid contraceptives were administered to induce an artificial menstrual cycle. At the closing stage of therapy clomiphene citrates were given in succession to restore the ovulatory cycle. Perspectives of administration of progestogens in young women with stage I endometrial carcinoma as a separate method of therapy are discussed.     

17-alpha hydroxyprogesterone caproate for preterm birth prevention: Where have we been,how did we get here,and where are we going?

Prematurity is a major public health problem in the United States and worldwide. Women with a history of a previous preterm birth are at high risk for recurrence. Progesterone is a key hormone involved in pregnancy maintenance. In general, progesterone is thought to maintain pregnancy through several closely linked mechanisms: (1) promotion of uterine quiescence, (2) inhibition of pro-inflammatory cells, and (3) immunosuppressive action. 17-Alpha hydroxyprogesterone caproate is currently the only medication approved to prevent recurrent preterm birth. The purpose of this review is to discuss the history of 17-alpha hydroxyprogesterone caproate use for recurrent preterm birth prevention, the rationale behind 17-alpha hydroxyprogesterone caproate administration, and current evidence-based indications for 17-alpha hydroxyprogesterone caproate use.     

Serum lipids and lipoproteins in patients with endometrial carcinoma receiving adjuvant treatment with hydroxyprogesterone caproate

Serum levels of triglycerides, total cholesterol, and HDL-cholesterol were determined in 57 patients who were undergoing treatment for stage I endometrial carcinoma. The patients belonged to a clinical trial where group A (control) was treated with surgery plus intravaginal irradiation, whereas group B in addition was treated with hydroxyprogesterone caproate (5000 mg i.m. as a loading dose followed by 1000 mg every 2 weeks for one year). In group B patients followed during the first 13 weeks of treatment, the level of serum triglycerides remained stable, whereas the level of total cholesterol and HDL-cholesterol increased significantly. This increase could not, however, have been caused by the progestogen treatment, as similar changes were seen in group A patients followed for the same period of time. Long-term effects were looked for in patient groups examined 3-12 months after the start of treatment and in groups examined 3-6 months after the hormone therapy was stopped. In neither group could any significant difference in cholesterol or HDL-cholesterol be found. It is concluded that this type of progestogen treatment causes no significant change in the levels of triglycerides, cholesterol, and HDL-cholesterol.     

First trimester endocrinology: consequences for diagnosis and treatment of pregnancy failure.

First-trimester endocrinology is determined on the one hand by corpus luteum progesterone and estradiol biosynthesis and secretion and on the other hand by the time of onset and extent of progesterone and estradiol secretion by the placenta. This dual interplay is dominated by the corpus luteum placental shift, where a relative progesterone and estradiol deficiency can develop and may lead to early as well as late abortion. Measurements of serum progesterone and estradiol are mandatory in order to reveal such deficiencies and to treat them effectively with 17 alpha-hydroxyprogesterone caproate in combination with estradiol valerate or with progestins such as dydrogesterone.     

Evaluation of endometrial steroid receptors and cell mitotic activity in women using copper intrauterine device: Can Cu-T prevent endometrial cancer?

AIMS: To study changes in endometrial proliferative indices (i.e. cell mitosis and Ki67), endometrial steroid (estrogen and progesterone) receptors, and serum estradiol and progesterone level in women using copper intrauterine device (IUD) after 6 months of use. METHODS: Fifteen healthy women were recruited having no contra indication to IUD or endometrial biopsy. Endometrial biopsies and serum samples were taken on 10/11th day of menstrual cycle at recruitment and after six months. The endometrial samples were subjected to: (i) steroid receptor estimation by immunohistochemistry; (ii) cell mitosis and Ki67 estimation by morphology and proliferative indices. RESULTS: The mean glandular mitotic index was 1.69 +/- (0.39) at first visit and 0.35 +/- (0.15) at second visit after 6 months. Similarly, Ki-67 count in glands was 11.79 +/- (1.59) at first visit and 2.40 +/- (0.54) at second visit. In the stroma, Ki67 decreased from a mean of 0.85 to 0.01 in six months. This suggested statistically significant reduction in proliferation and mitotic activity in endometrial glands and the stroma of women who used Cu-T continuously for a long period.There was a significant reduction of estrogen receptor concentration in glands (from a mean of 51.67 down to 11.67) and the stroma (from a mean of 33.00 to 8.00) over this 6-month period. The observed fall in progesterone receptor counts was less compared to other parameters studied, being marginally significant in stroma (from a mean of 32.00 down to 14.33), but not significant enough in glands (from a mean of 45.00 down to 25.00). No changes were observed in serum hormone levels in these two visits. CONCLUSION: Continuous use of copper intrauterine device causes significant reduction in endometrial mitotic activity as well as estrogen receptor concentration without affecting serum estradiol or progesterone levels. This finding infers that Cu-T may have a protective role against endometrial cancer.     

Effects of clomiphene citrate on cytosolic estradiol and progesterone receptor concentrations in secretory endometrium

Cytosolic estradiol and progesterone receptor concentrations were measured in luteal phase endometrial biopsy samples obtained from 12 anovulatory or oligoovulatory women on clomiphene citrate therapy and from 40 normal control subjects. Clomiphene citrate treatment (250 to 750 mg per cycle) decreased both endometrial estradiol and progesterone receptor concentrations. Estradiol receptor levels were nondetectable in seven tissue samples and progesterone receptor levels in four samples from the 12 subjects given clomiphene citrate compared to nondetectable estradiol receptor concentrations in one tissue sample and progesterone receptor concentrations in two samples from the 40 normal control subjects. In histologically dated endometrium, mean estradiol receptor concentrations on days 20 to 23 and progesterone receptor levels on days to 24 to 27 were lower than the values observed in the comparable dated endometrium of normal ovulatory women. Steroid receptor concentrations correlated negatively with the duration of clomiphene citrate therapy, which implies a time-dependent suppressive effect of clomiphene citrate on measurable cytosolic estradiol and progesterone receptor concentrations during the luteal phase of the cycle.     

Elaboration of a working model for the involvement of inhibin A as a mediator of the preovulatory rise of progesterone levels.

During the final days of follicular development, exogenously administered follicle-stimulating hormone (FSH) produces a rise in serum progesterone level. The aim of the present study was to investigate the possible source and regulation of this preovulatory progesterone surge. Four sets of matching treatments with gonadotropins for in vitro fertilization and intracytoplasmic sperm injection were selected from a cohort of 953 treatments in 244 couples. Half of these four sets of treatments were selected based on the unusual course of the progesterone concentration during follicular development. The first set of 11 cycles with early termination of gonadotropin administration for prolonged coasting were compared with a set of 12 cycles with similar estradiol levels but with uninterrupted ovarian stimulation. Another set of 12 cycles with low preovulatory progesterone levels (<2 nmol/l) were matched with ten cycles with normal preovulatory progesterone levels (>2 nmol/l). The sera of these four selected sets of treatments were stored for subsequent measurement of the concentrations of inhibin A, inhibin B, activin A and leptin. During ovarian hyperstimulation serum levels of inhibin A correlated significantly with those of progesterone (p < 0.001), whereas this correlation disappeared after the withdrawal of FSH administration. The rapid fall of progesterone levels during prolonged coasting contrasts with the continuing rise of estradiol concentration and indicates that the theca interna, not the granulosa, is the major source of preovulatory progesterone. Women failing to produce any increment of progesterone levels at the end of follicular development had significantly lower levels of inhibin A (p < 0.05), indicating that inhibin A may well be involved in mediating the signal of FSH from the granulosa to the theca interna.     

Endometriosis: role of ovarian steroids in initiation, maintenance, and suppression

Although endometriosis is commonly associated with infertility, the hormonal requirements for its spontaneous initiation and maintenance remain unknown. Since endometriosis occurs in the monkey, these primates are useful for examining the hormonal dependencies of endometrial plaques. Sequential estradiol and progesterone in Silastic capsules were placed subcutaneously into long-term castrated monkeys (N = 26). Blood samples obtained biweekly were assayed for progesterone and estradiol by radioimmunoassay. Three weeks later, endometriectomies were performed and the minced endometrium was "seeded" into the peritoneal cavity. Thereafter, monkeys were divided into four groups: (1) control, received no therapy; (2) received only estradiol capsules; (3) received only progesterone capsules; and (4) received both estradiol and progesterone capsules. All monkeys underwent laparotomy 4, 12, and 16 weeks after endometrial transplantation to determine whether viable endometrial plaques were present. After 4 weeks, endometriosis was found in all groups, including the controls. At 12 and 16 weeks, monkeys treated with both estradiol and/or progesterone contained viable endometrial plaques, whereas monkeys without steroid supplementation contained only "burnt out" plaques, that is, nonviable endometrial tissue. In conclusion, endometrial tissue transplanted into the peritoneum required no steroid supplementation for initiation. However, once implanted, either estradiol or progesterone, alone or in combination, was required for maintenance. These findings suggest that successful treatment of endometriosis may require both the eradication of existing endometrial plaques and the prevention of reseeding over the peritoneum resulting from retrograde menstruation.