Response to repetitive cycles of ovulation induction in the same women

It has been theorized that the administration of human menopausal gonadotropin (hMG) in consecutive menstrual cycles will result in a poor follicular response in the second cycle. To examine this, 50 women undergoing ovulation induction in two consecutive cycles were assessed, using in each the same induction regimen during the initial 5 days. The remainder of each cycle was individualized according to their response. Nine women were anovulatory, 19 were oligoovulatory, and 22 ovulated regularly in unstimulated cycles. In repeat cycles only 3 of 50 had poor follicular development and did not receive human chorionic gonadotropin (hCG); all were anovulatory. Forty-two of 50 of the first cycles had continually rising estradiol (E₂), while 43 of 47 of the second cycles had rising E₂ patterns. Grouping the peak E₂ prior to hCG in the ranges <300, 300–699, 700–1099, and 1100 pg/ml, peaks in the second cycle were similar in 25 of 50, lower in 16, and higher in 9. Only 3 of 9 anovulatory women had similar peaks, as compared to 22 of 41 of the oligoovulatory and regularly ovulating women. Comparing the second to the first cycle, the day of hCG was within 1 day in 28 of 50 women, 2 or more days less than the first cycle in 6, and 2 or more days greater than the first cycle in 11. We conclude that in a successive cycle of ovulation induction (i) the follicular response is impaired in anovulatory women, but (ii) in oligoovulatory or regularly ovulating women, clinically significant differences in the estradiol response do not occur.     

Levels of oxytocin-like activity and progesterone in follicular fluid from in vitro fertilization cycles

Oxytocinlike immunoreactivity, estradiol, and progesterone were measured in follicular fluid collected during oocyte collection in an in vitro fertilization program in which clomiphene citrate was used to stimulate follicular development. Follicles which yielded morphologically normal embryos after fertilization of the oocyte had oxytocin concentrations ranging from <10 to 600 ng/liter. Oxytocin concentrations did not differ between follicles from 12 pregnancy cycles (median, 169; N=21 and follicles from 12 nonpregnancy cycles (median, 110; N= 18). Oxytocin concentrations were correlated negatively with progesterone concentrations (Spearman's rank correlation coefficient r=–0.50; P=0.001). In cycles with some follicles having progesterone concentrations <10 and some >10 mol/liter, oxytocin concentrations were higher in the less progestogenic follicles in 15 of 16 cases.     

Development of a synthetic peptide-based tartrate-resistant acid phosphatase radioimmunoassay for the measurement of bone resorption in rat serum

Selective markers of bone turnover provide a convenient and reproducible alternative to the complex and expensive histochemical techniques used commonly to study the effect of pharmacological agents and the pathogenesis of bone disease in the ovariectomized (OVX) rat model. One marker, which has been specifically linked to terminally differentiated osteoclasts and, thus, provides useful insight at cellular levels, is type-5 tartrate-resistant acid phosphatase (TRACP). We describe the development of a TRACP radioimmunoassay (RIA), which requires synthetic peptide for antibody development. To develop the RIA, polyclonal antibodies were generated in goats against a synthetic peptide, DPSVRHQRKCY, corresponding to amino acid residues 267–275 of the rat type-5 TRACP sequence. In the RIA, 50 μl of rat serum, 100 μl of goat anti-TRACP antibodies, and 100 μl of tracer were incubated overnight. The antibody-bound fraction was separated, counted, and unknown values were calculated by comparison with the peptide calibrator. Rat serum shows parallelism with the synthetic peptide calibrator used in the RIA. The sensitivity of the RIA was 24.7 μg/l, and the measuring range was 19–2476 μg/l. The average intra-assay coefficients of variation for (CV) two controls were less than 7%. The average dilution and spike recoveries were 107% and 87%, respectively. We applied our peptide-based RIA to study bone resorption in an OVX rat model. TRACP concentrations in serum in 12-week-old OVX Sprague Dawley rats were 14%–22% (P < 0.05) higher than those in the sham-operated rats, and TRACP concentrations in OVX rats treated with estradiol were 24%–32% lower (P < 0.01) than those in the vehicle-treated OVX group. Similarly, as compared with those in OVX rats, TRACP concentrations decreased to those of sham levels in OVX rats receiving 10 μg/kg per day of alendronate for 10 days. In addition, the TRACP levels determined by RIA showed a significant correlation with serum C-telopeptide (type-I collagen) concentrations (r = 0.56; P < 0.001) measured by an enzyme-linked immunosorbent assay (ELISA) developed earlier for the rat model. In conclusion, we have developed a TRACP RIA that could be used to monitor the rate of bone resorption in the rat model. Received: June 18, 2001 / Accepted: October 26, 2001     

Effect of clofibrate administration on the esterification and deesterification of steroid hormones by liver and extrahepatic tissues in rats

Treatment of rats with clofibrate markedly stimulated the liver microsomal esterification of estradiol, testosterone, pregnenolone, dehydroepiandrosterone, and corticosterone by acyl-CoA:steroid acyltransferase. This enzyme catalyzes the esterification of estradiol with long-chain fatty acids in both liver and extrahepatic tissues. In untreated control rats, brain had the highest acyltransferase activity per milligram of microsomal protein for estradiol esterification (3- to 4-fold higher than in the liver). Although, treatment of rats with clofibrate stimulated the esterification of estradiol by 9- to 14-fold in the liver, estradiol esterification in kidney, lung, brain, uterus, fat, and mammary glands was not increased, indicating that liver may be uniquely sensitive to induction of acyl-CoA:estradiol acyltransferase by clofibrate. In additional studies, esterase activity for hydrolysis of the oleoyl ester of estradiol was determined in control and clofibrate-treated rats. Clofibrate administration increased esterase activity by an average of 107% in fat and 70% in liver. The results indicate that treatment of rats with clofibrate stimulates the hepatic formation of highly lipophilic fatty acid esters that can be hydrolyzed in the liver and in extrahepatic tissues to the parent steroid hormone by a clofibrate-inducible esterase.     

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers.In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.     

雌激素抗肾上腺素实验性心律失常作用

目的： 探讨雌激素在整体水平下的抗肾上腺素心律失常作用及可能机制.方法：24只新西兰大白兔随机分为对照组、利多卡因组及雌激素组,各组同步记录体表心电图及经左心室插管测定心功能指标[ 左心室内压（LVSP）、左心室舒张终末压（LVEDP）、左心室内压最大上升速率（＋dp/dtmax）、左心室内压最大下降速率（-dp/dtmax） ], 比较各组按75 μg/kg 静脉注射0.1%肾上腺素前后心电图及相应心功能指标变化.结果：快速静脉注射肾上腺素可引起心功能指标明显上升,同时由于自律性增高致室性心律失常;雌激素可拮抗肾上腺素所致心功能改变,并延长室早（VP）出现时间,缩短室速（VT）持续时间及心律失常持续时间,其作用优于利多卡因（P〈0.05）.结论： 雌激素对心律失常有一定对抗作用,可能与Ca^2＋阻断及改变细胞膜离子通透性有关.     

Dysfunctional uterine bleeding in adolescence

This paper assesses the basic steps of management and treatment of dysfunctional uterine bleeding (DUB) - the irregular bleeding arising from anovulation. After menarche, the hypothalamic-pituitary-ovarian axis can take several years to mature resulting in anovulatory and therefore irregular cycles. During an anovulatory cycle, the corpus luteum fails to form, causing failure of normal cyclical progesterone secretion. This results in continuous unopposed production of estradiol, stimulating overgrowth of the endometrium. Without progesterone, the endometrium grows thicker and thicker eventually outgrowing its blood supply, leading to necrosis. The end result is very heavy bleeding.     

单纯性肥胖男生血清瘦素、性激素水平及性发育调查

目的:研究男性血清瘦素水平与单纯性肥胖、青春期性发育的关系。方法: 49名 8~16岁单纯性肥胖男生和 44名正常男生按年龄划分为 8~岁、11~岁和 14~16岁 3个年龄段,采用放射免疫法对各组男生进行血清瘦素、睾酮、雌二醇含量定量测定,同时进行首次遗精时间调查。结果:肥胖组各年龄段血清瘦素水平均高于正常组(P<0. 05或 0. 01);随着年龄增长,肥胖组男生血清瘦素水平呈现先上升后下降的变化趋势,在 11~岁年龄段达最高值;而正常组男生血清瘦素水平随着年龄增长则呈现下降的趋势。肥胖组男生首次遗精时间 (12. 5±1. 2)岁,早于正常组男生(13. 2±1. 2)岁(P<0. 01)。雌二醇水平在 11~岁年龄段,肥胖组低于正常组(P<0. 05)。睾酮水平各年龄段,肥胖组与正常组比较,差异均无统计学意义(P>0. 05)。肥胖组男生睾酮与瘦素呈负相关 (r=-0. 33,P<0. 05)。结论:单纯性肥胖男生血清瘦素水平偏高;持续高浓度的瘦素水平可能对男性性发育产生一定的负面影响。     

SLE发病机制中雌激素与细胞因子之间的关系

目的：探讨系统性红斑狼疮（SLE）外周血单个核细胞（PBMC）经雌二醇（E2）刺激前后TNFα和IL-6水平变化的相关性。方法：提取SLE患者（患者组）及健康志愿者（对照组）的PBMC，用酶联免疫吸附法（ELISA）测定上清液在E2刺激前后的肿瘤坏死因子α（TNFα）和白细胞介素6（IL-6）水平。结果：患者组有或无E2刺激的PBMC分泌的TNFα水平均高于对照组（P〈0．01），患者组E2刺激后PBMC分泌的TNFα水平低于无E2刺激时（P〈0．05），而对照组E2刺激前后TNFα水平无明显变化（P〉0．05）。无E2刺激的PBMC分泌的IL-6水平患者组高于对照组（P〈0．05），患者组有E2刺激PBMC分泌的IL-6水平与对照组比较差别无统计学意义（P〉0．05）。2组PBMC在E2刺激后分泌的IL-6水平均降低（均P〈0．05）。结论：TNFα和IL-6水平可以作为SLE疾病活动的监测指标，高水平的E2对SLE的PBMC分泌TNFα和IL-6都有明显抑制作用。TNFα的降低可能提示为SLE活动期。