围着床期过度增厚的子宫内膜对其胚胎容受性的影响

目的:通过研究人过度增厚的子宫内膜围着床期整合素β3和白血病抑制因子表达的变化以探讨其对子宫内膜容受性的影响。方法:采用化学发光法、免疫组织化学技术分别检测20例过厚子宫内膜者黄体中期血清雌二醇(E2)、孕酮(P)水平以及子宫内膜整合素β3和白血病抑制因子(LIF)的表达,同期25例正常子宫内膜者进行对照。结果:两组血清E2、P水平比较差异无统计学意义(P>0.05);研究组整合素β3和白血病抑制因子的表达均明显低于对照组(P<0.01)。结论:过度增厚的子宫内膜可能通过围着床期内膜容受性标志物——整合素β3和白血病抑制因子表达降低引起其容受性下降。     

Norplant使用者子宫内膜血管内皮生长因子、碱性成纤维细胞生长因子及转移生长因子β_1的研究

为探讨Norplant使用者子宫不规则出血的相关因素,对使用Norplant月经规律和有不规则子宫出血者的子宫内膜与正常子宫内膜的形态、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)及转移生长因子β1(TGFβ1)进行比较观察。结果显示:Norplant使用者子宫内膜无典型的周期特点,子宫内膜VEGF比正常子宫内膜减少,尤其是不规则出血组减少更为明显,但bFGF及GFβ1无明显差异。提示Norplant使用者子宫异常出血与子宫内膜VEGF的减少有关。     

阴道超声测量绝经前妇女子宫内膜厚度诊断子宫内膜病变

目的:探讨阴道超声测量子宫内膜厚度是否可用于预测绝经前妇女子宫内膜病变。方法:对87例绝经前不规则子宫出血患者行阴道超声测量子宫内膜厚度并于检查当日或次日行分段诊刮术,将阴道超声检查结果与诊刮获取的子宫内膜组织病理结果进行比较。结果:阴道超声测得子宫内膜癌及癌前病变组的内膜平均厚度为(27.3±11.0)mm,子宫内膜良性病变组的内膜平均厚度为(15.5±4.8)mm,均明显大于子宫内膜生理改变组的内膜平均厚度(9.8±4.3)mm,差异均有极显著性意义(P<0.0001)。以10mm为临界值阴道超声预测绝经前妇女子宫内膜病变的敏感性、特异性、阳性预测值、阴性预测值分别为95.9％、57.9％、74.6％和91.7％。结论:阴道超声测量子宫内膜厚度以10mm为临界值可以预测绝经前妇女子宫内膜病变。     

子宫自然杀伤细胞的研究进展

存在于子宫内膜层面的子宫自然杀伤细胞（uNK细胞）与女性月经周期、妊娠免疫、子宫不规则出血等多种生殖内分泌过程有关，该文就uNK细胞的研究进展进行相关综述。     

Pharmacokinetic and pharmacodynamic studies of levonorgestrel-releasing intrauterine device

Intrauterine devices releasing 20 micrograms/day levonorgestrel were inserted in 10 women (ages 25-34). Bleeding and spotting patterns were recorded on a menstrual card during one year of follow-up. Blood samples were collected for radioimmunoassays of LH, estradiol (E2), progesterone (P) and levonorgestrel (LNG) and for sex hormone binding globulin (SHBG) 3 times a week during the 1st month of use, and twice a week during the 6th and 12th treatment months. Among the 10 women, two experienced irregular cycles with prolonged intermenstrual spotting, four had amenorrhea in the latter part of treatment months, while the other four had regular cycles. According to the serum levels of E2 and P, the hormone profiles were divided into four types of reaction: A) anovulatory, B) anovulatory but with high follicular activity, C) ovulatory but with luteal insufficiency, and D) ovulatory. Among the 29 treatment cycles, there were 10 D-type, 3 C-type, 13 B-type and 3 A-type of ovarian reactions: 44.8% of the cycles were ovulatory (C + D) and 55.2% were anovulatory (A + B). In general, serum levels of levonorgestrel were low in ovulatory cycles and were high in anovulatory cycles. The difference was statistically significant. There were marked individual differences. The decline of serum LNG from the 1st (492 pmol/l) to the 6th (320 pmol/l) treatment months was 34.9% on average. The amenorrheic cycles coincided mostly with the hormonal profile of ovulatory types, which indicated that the cause of amenorrhea is due to the local effect of levonorgestrel on the endometrium. The levonorgestrel levels were significantly correlated with serum SHBG, r = 0.8856, p less than 0.001, and with E2, r = 0.4661, p less than 0.05.     

Endometrial carcinoma in the young]

The authors aim is to draw the readers attention to the possible occurrence of endometrial carcinoma in the young, by presenting the case of a 23 year-old woman. They highlight the risk factors (obesity, anovulatory bleeding abnormality, hypertension, positive familial history), that may have lead to the development of the endometrial carcinoma of their patient. It is assumed, that bleeding abnormality of a young woman could be the first sign of the carcinoma of the uterine corpus. They consider it obligatory in similar cases to: 1. Perform a throughout investigation of the endocrinological status 2. Measure the thickness of the endometrium with ultrasound 3. Histological examination 4. Careful follow up.     

天然孕酮对绝经期子宫内膜增厚的治疗效果评价

目的探讨天然孕酮在绝经期子宫内膜增厚治疗中的临床应用价值。方法对102例绝经期女性B超提示子宫内膜增厚者进行天然孕酮胶丸口服治疗,200 mg/d,共12 d,停药2周后观察子宫内膜厚度变化。结果 83例治疗后内膜转为正常厚度,有效率81.37%,差异有统计学意义(P<0.05)。治疗后有阴道流血病例的内膜转化有效率高于无阴道流血病例,差异有统计学意义(P<0.05)。19例无效者行诊断性刮宫术,其中4例为萎缩性子宫内膜,6例为分泌期子宫内膜,4例为子宫内膜单纯性增生,2例为子宫内膜不典型增生,3例为子宫内膜息肉。用药后无效者中无阴道流血患者病理性子宫内膜例数明显多于有阴道流血的例数,差异有统计学意义(P<0.05)。结论口服天然孕激素治疗作为绝经后妇女单纯子宫内膜增厚的治疗手段是有效的,对用药后无阴道流血的内膜增厚病例进行诊断性刮宫术,可提高子宫内膜病变的检出率。     

The effects of chronic administration of LH-RH agonists and antagonists on the menstrual cycle and endometrium of the rhesus monkey

Regularly cycling rhesus monkeys (Macaca mulatta) were used to study the effects of prolonged administration of LH-RH analogs on the menstrual cycle and the endometrium. According to the treatment, animals were divided into: Group 1, vehicle; Group 2, LH-RH agonist (D-Trp6 LH-RH, 20 micrograms/day); and Group 3, LH-RH antagonist [( N-Ac-D-Trp1,3, D-p-Cl-Phe2,D-Arg6,D- Ala10 ]-LH-RH,200 micrograms/day) for 90 days. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P) were measured every second day until thirty days past the discontinuation of drug administration. Endometrial biopsies were obtained on days 10, 40, 90 and 120 and processed for histologic exam and determination of estrogen (E) and progesterone receptors. Animals of Group 1 presented regular cycles, while those in Groups 2 and 3 remained anovulatory throughout the treatment. Animals of Group 2 presented different degrees of endometrial hyperplasia during treatment and animals of Group 3 showed either resting or atrophic endometrium. Administration of LH-RH agonist produced a marked increase in E and P endometrial receptors and the antagonist produced a decrease in P receptors. In both instances, reversal of the effects on the menstrual cycle and in the endometrium was observed 30 days after discontinuation of drug administration.     

Contraception with a norethisterone-releasing IUD. Plasma levels of norethisterone and its influence on the ovarian function

Five healthy women had a norethindrone (NET)-releasing intrauterine device inserted postmenstrually. During a treatment time ranging between 80 and 114 days, plasma concentrations of NET, estradiol, and progesterone were determined by radioimmunoassay. Initial high plasma concentrations of NET were followed by fairly constant levels between 200 pg/ml and 400 pg/ml. Ovulation occurred regularly during nine out of sixteen studied treatment cycles, four cycles were anovulatory and three cycles showed a suppressed luteal phase. High estradiol peaks in plasma were seen at the time of disturbed ovulation. The bleeding pattern was regular and the menstrual bleeding was reduced in amount.     

Morphometric studies of the endometrium, the fallopian tube and the corpus luteum during contraception with the 300 micrograms norethisterone (NET) minipill

Biopsy specimen from endometrium, Fallopian tube and corpus luteum were obtained from 35 women treated with 300 micrograms norethisterone daily and from 10 untreated, normally menstruating women. Peripheral levels of LH, progesterone and estradiol were measured. In the norethisterone-treated women four different ovarian reactions were identified. Ovarian activity was completely suppressed (Type A) in 3 women, follicular activity only (Type B) in 10 women, follicular activity was followed by insufficient luteal function (Type C) in 12 women, and peripheral estradiol and progesterone levels compatible with normal ovulation (Type D) in 10 women. The histology of the endometrium varied between atrophy (3 subjects), suppressed proliferation (9 subjects), proliferation (8 subjects), irregular secretory changes (12 subjects) and apparently normal secretory activity (3 subjects). When the histology of endometrium and Fallopian tube was compared with the peripheral hormonal levels and the corpus luteum steroid production in vitra, no correlation was found. Nor was a correlation found between the histologic changes of corpus luteum, endometrium and Fallopian tube. Thus, these target organs seem to react independently to norethisterone treatment.     

Induction of menstruation by antiprogesterone ZK 98.299 in cycling bonnet monkeys

The antiprogestin ZK 98.299 (11 beta-(4-dimethylaminophenyl)-17 alpha-hydroxy-17 beta-(3-hydroxypropyl)-13 alpha-methyl-4,9-gonadien-3-one) was administered s.c. (30mg/day) to two groups of cycling bonnet monkeys. In Group I (n = 6), it was injected from day 16 to 18 and in Group II (n = 9) from day 21 to 23 of the cycle. Each animal served as its own control and in the pretreatment cycle the vehicle (benzyl benzoate: castor oil, 1:4) was administered. During the treatment cycle of these animals the peak in estradiol levels was observed between days 8 to 11 of the menstrual cycle. In Group I animals, administration of ZK 98.299 induced vaginal bleeding in three of the six animals within two days of its first injection. In the remaining three animals the menstrual cycle length was prolonged. However, in all the six animals a premature drop in serum progesterone levels was observed. On the other hand, in Group II in seven animals with ovulatory treatment cycles, administration of ZK 98.299 induced vaginal bleeding within four days of the first dose and significantly shortened the cycle length. A significant decline in progesterone levels was observed in these animals also. However, in two animals in each group, ZK 98.299 induced vaginal bleeding while the serum progesterone levels were still high. Post-treatment cycles were ovulatory but the cycle length was marginally increased in some animals. In two animals of Group II, in which the treatment cycle turned out to be anovulatory, ZK 98.299 did not induce bleeding and had no effect on serum progesterone levels. This study shows that when administered during the luteal phase ZK 98.299 induces vaginal bleeding and premature luteal regression in bonnet monkeys. However, induction of vaginal bleeding may not be associated with drop in progesterone levels. ZK 98.299, therefore, appears to have potential for fertility control which warrants clinical evaluation.     

妈富隆治疗无排卵型功血37例

目的　探讨治疗无排卵型功血的简单、有效的方法。方法　将37例无排卵型功血分为2组,分别服用炔诺酮(妇康片)和妈富隆治疗,观察疗效。结果　妈富隆组完全止血时间平均为2 0 .7小时,快于妇康片组。P <0 .0 1。结论　妈富隆治疗无排卵型功血方法简便,止血迅速,副作用小。     

A comparative study of Cyclofem and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature

OBJECTIVES: The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem, was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding. METHODS: Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques. RESULTS: Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 +/- 6.7 (mean +/- SD)/mm(2) before injection. This significantly decreased to 132.4 +/- 12.2 after DMPA use, and from 151.9 +/- 5.8 to 131.8 +/- 12.8 vessels/mm(2) following Cyclofem use (paired t-test, p <0.05). However, there was no significant difference between endometrial vascular density during treatment with Cyclofem or DMPA. Total bleeding days in the first and second 3-month time intervals were 28 +/- 23 and 18 +/- 12 days in DMPA users and 22 +/- 14 and 16 +/- 9 days in Cyclofem users, respectively, Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups. CONCLUSIONS: This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women.     

A morphometric study of the effect of oral norethisterone or levonorgestrel on endometrial blood vessels

A morphometric study was undertaken to quantitate vessel numbers in uterine biopsies from a control group of patients, patients with dysfunctional uterine bleeding and patients taking low dose norethisterone or levonorgestrel. Vessels were counted at the endometrial/myometrial junction and in the functional endometrium just below the surface epithelium. The number of arteries at the endometrial/myometrial junction was found to be decreased in patients taking norethisterone and levonorgestrel. An increase was found in the total number of veins and in the number of dilated veins in the functional endometrium of the progestogen-treated specimens. Dilated veins were frequently found close to the endometrial surface and it is possible that they may be the major cause of the irregular bleeding associated with low dose oral progestogens.     

The prospects for hormonal sterilization

Any contraceptive method acts by producing temporary sterility. Var iations in the time of spontaneous ovulation and variations in the length of the cycle render the date of ovulation relatively unpredictabl e. The safe period, therefore, varies. Hormonal sterilization deals with methods that render the woman sterile for the duration of at least 1 menstrual cycle. This anovulatory cycle is 1 method. No corpus luteum forms although bleeding occurs cyclically. Most cycles during lactation are sterile. Other women sometimes have anovulatory cycles. Prolactin injections have been shown to temporarily suppress ovarian cyclic activity in mice and rats. Prolactin may produce anovulatory cycles in women and thus provide a method of hormonal sterilization. 4 mg progesterone daily inhibits estrus. Studies with estrone show that it has a depressant effect on ovarian response to follicle stimulating hormone. Large doses of estradiol benzoate used to treat dysmenorrhea have altered menstrual rhythm. Injection of gonadotrophic antisera for prevention of ovulation is a possibility. Daily injections of estrone, begun on day of mating, usually have resulted in retention of ova in the fallopian tubes of mice and rabbits. All of these ova showed signs of degeneration by Day 4. Fertilized human ova may be tube locked by an excess of estrone or degeneration of the fertilized ovum may inhibit further development. The potentialities of hormonal sterilization are great. Extensive investigation for humans is warranted.     

Pharmacokinetic and pharmacodynamic studies of vaginal rings releasing low-dose levonorgestrel

Pharmacokinetic and pharmacodynamic effects of a vaginal ring releasing 20 micrograms/day levonorgestrel (L-NOG) have been studied in 15 women. Serum levels of L-NOG, estradiol and progesterone were measured three times a week in a control menstrual cycle and a treatment period of 3 months after the insertion of the first vaginal ring. All control cycles were normal ovulatory. Among the 36 treatment cycles 13 were ovulatory (36%), 5 ovulatory with inadequate luteal function (14%), 14 anovulatory but with marked follicle activity (39%) and 4 anovulatory (11%). In the groups with ovulatory reaction the serum levels of L-NOG showed a decline of 54% of the initial level at the end of the treatment period, calculated according to the linear regression equation of Y = 0.903-0.0142X, while in the groups without ovulation the L-NOG levels were higher and the decline was 24% of the initial level (Y = 1.034-0.0086X). There were distinct individual differences in the levels of L-NOG and ovarian reactions. Marked follicle activity with very high estradiol levels were found in correlation with high L-NOG in 7 treatment cycles, particularly in the B type of reaction (B = anovulatory cycle with marked follicle activity). More intermenstrual bleeding and spotting occurred in the second treatment cycles, particularly in those with anovulatory reactions.     

Influence of the LH-RH analogue buserelin on cyclic ovarian function and on endometrium. A new approach to fertility control?

The long-acting stimulatory luteinizing hormone - releasing hormone analogue D-Ser(TBU)6-EA10-LH-RH (buserelin) was administered intranasally once daily in a dose of 400 mcg to 24 normally ovulating women and to 4 women with pre-existing endocrine dysregulation. Ovulation was inhibited in 136 out of 156 treatment months. In 20 treatment months, progesterone values temporarily increased indicating luteinization of follicles or ovulation with defective corpus luteum function. Estradiol secretion showed a tendency to lower values as treatment progressed but individually indicated follicle maturation until the end of the observed medication period. Bleeding pattern ranged from menses-like bleeding in regular as well as irregular intervals to amenorrhea. The morphological findings of 31 endometrial biopsies of 20 volunteers ranged from atrophy (n = 4) to proliferation (n = 25) with early signs of hyperplasia as well as early secretory transformation (n = 2). The morphological alterations indicate that unopposed estrogen stimulation of the endometrium is the main problem of long-term contraception with the dose schedule of buserelin used.     

绝经后阴道流血或流液超声检查的诊断价值

目的:探讨绝经后阴道不规则流血或流液患者的超声影像对绝经后子宫内膜癌患者的诊断价值。方法:对42例绝经后阴道不规则流血或流液患者的子宫内膜超声影像进行回顾,分析其子宫内膜的厚度。结果:其中子宫内膜厚度≥5 mm且病理诊断为子宫内膜癌的患者有27例,符合诊断率72.97%,50～59岁年龄段中子宫内膜癌的发病率较其他年龄段高。结论:超声检查可作为子宫内膜癌及诊断性刮宫前重要的筛查方法,对临床上制定个体化治疗方案提供重要依据。     

A D-norgestrel-releasing IUD.

Steady release of d-norgestrel from an IUD was achieved with a plain Tatum-T-device, the carrier material being sleeves of silastic^R. The device was tested in six healthy women, and plasma concentrations of d-norgestrel, estradiol and progesterone were determined for periods of 112–114 days. The values found corresponded to a daily release of 50 μg d-norgestrel. This amount was enough to suppress ovulation. The bleeding pattern was irregular, but the amount of bleeding was reduced. Biopsies showed endometrial hypofunction. The advantage of the intrauterine route of administration of d-norgestrel is discussed.     

Injectable depot contraceptives on d-norgestrel basis II. Clinical pharmacokinetic studies with d-norgestrel undecylate in women

The effect of a single intramuscular injection of 100 mg of d-norgestrel 17β-undecylate was investigated in 8 women. Levels of radioimmunoassayable serum progesterone, 17β-estradiol and d-norgestrel were studied for at least three months. Besides registration of uterine bleeding, in 5 out of these 8 subjects karyopyknotic index (KI) and cervical function (CF) was recorded. Six patients showed a maximum of d-norgestrel serum levels between 400 and 700 pg/ml 24–48 hr after injection of the d-norgestrel ester. Thereafter, the values dropped to constant levels varying between 50 and 150 pg/ml, and stayed at these levels for at least 130 days. Two subjects showed maximal dnorgestrel serum levels of 1300 and 1500 pg/ml 10 and 19 days, respectively, after injection. In this group d-norgestrel serum levels stayed at 300 pg/ml for 100 days after treatment. All 8 patients had normal pretreatment cycles. Two patients had normal first treatment cycles followed by anovulatory cycles. All other subjects had anovulatory first treatment cycles, which were followed by ovulatory cycles. Poor bleeding control was registered in all patients. The data suggest a slow release of the ester from the depot and an insufficient cleavage of the ester into d-norgestrel and fatty acid resulting in a low and varying progestagen bioavailability.