雌孕激素用于减少药物流产后阴道出血的疗效观察

目的 比较不同种类和剂量的雌孕激素减少药物流产后阴道出血的临床疗效.方法 将对象随机分为复方短效口服避孕药组(COC组)于胚囊排出当日起口服去氧孕烯炔雌醇片1片/d,连服21 d;雌孕激素序贯治疗组(E+P组),于胚囊排出当日起口服戊酸雌二醇片2 mg/d,连服21 d,最后5d同时加服醋酸甲羟孕酮片10 mg/d;对照组不服用雌孕激素类药物.比较3组药物流产后阴道出血、月经恢复以及药物流产结局.结果E+P组与对照组相比药物流产后出血天数明显缩短,分别为(14±7)d和(19±11)d,P＜0.01,而COC组为(20±13)d,与对照组相比差异无统计学意义(P＞0.05).3组阴道出血量的差异无统计学意义(x2=1.274,P＞0.05).转经天数E+P组为(30 ±7)d、COC组为(34 ±13)d,分别与对照组(39 ±11)d相比差异有统计学意义(P＜0.05),但E+P组与COC组间的差异无统计学意义(P＞0.05).3组间不全流产发生率的差异无统计学意义(X2 =1.465,P＞0.05).结论 药物流产后应用雌孕激素序贯治疗能有效减少药物流产后阴道出血时间,而复方短效口服避孕药对减少阴道出血的疗效不明显,但二者均能有效促进药物流产后恢复,且疗效相似.     

Serum pharmacokinetics of orally administered desogestrel and binding of contraceptive progestogens to sex hormone-binding globulin

Serum levels of 3-ketodesogestrel and ethinyl estradiol were analyzed by radioimmunoassay in a balanced crossover study with two tablet formulations containing desogestrel (0.150 mg) and ethinyl estradiol (0.030 mg) in 25 women under steady-state conditions after 21 days of treatment. The pharmacokinetic properties of desogestrel were characterized by the following parameters: (1) maximum serum concentration, (2) time to maximum serum concentration, (3) total area under the serum concentration versus time curve, and (4) serum half-life of elimination. The interindividual variation in these parameters was comparable with that observed with other contraceptive combinations containing ethinyl estradiol and norethisterone, levonorgestrel, or gestodene. The serum distribution of contraceptive progestogens is known to be determined by their affinity to sex hormone-binding globulin and the concentration of sex hormone-binding globulin. We analyzed the structural features that determine binding to sex hormone-binding globulin. The 18-methyl group increased and the 11-methylene group weakened the binding to sex hormone-binding globulin. The double bond at C-15 reinforced the binding only when combined with an 18-methyl group. Therefore, the binding of levonorgestrel (the 18-methyl derivative of norethisterone) and gestodene (the Δ-15,18 methyl derivative of norethisterone) to sex hormone-binding globulin was much stronger than that of 3-keto-desogestrel and norethisterone.     

去氧孕烯炔雌醇片辅助治疗卵巢子宫内膜异位症腹腔镜术后复发的效果分析

【摘要】目的探讨口服避孕药去氧孕烯炔雌醇片用于辅助治疗卵巢子宫内膜异位症（EMT）腹腔镜术后复发的疗效和安全性。方法将90例EMT患者分成口服避孕药去氧孕烯炔雌醇片组（A组）、孕三烯酮组（B组）、单纯手术组（C组）。分别比较各组患者治疗后的各项指标以评价效果。结果A组与B组复发率差异无统计学意义（P〉0．05）,两组复发率均显著低于C组,但A组不良反应发生率最低（P〈0．05）。3组性激素水平与CAl25水平均有下降,A组下降最明显,差异有统计学意义（P〈0．05）。结论去氧孕烯炔雌醇片用于辅助治疗EMT腹腔镜术后复发与孕三稀酮疗效相当,但具有不良反应轻、价格低廉等优点。     

去氧孕烯炔雌醇治疗绝经过渡期功能失调性子宫出血的临床疗效及对血清性激素水平的影响

目的探讨去氧孕烯炔雌醇治疗绝经过渡期功能失调性子宫出血（功血）的临床疗效及对血清性激素水平的影响。方法选择2010年4月至2012年10月在本院治疗并确诊为绝经过渡期功血患者94例,随机分为观察组和对照组,各47例。观察组在诊断性刮宫术后3天给予去氧孕烯炔雌醇治疗,对照组在诊断l生刮宫术后3天给予醋酸甲羟孕酮片治疗。对比观察两组止血时间、临床疗效和药物不良反应。检测患者治疗前后促卵泡生成素（FSH）、黄体生成素（LH）、雌激素（E：）的水平。结果观察组临床疗效总有效率为97．87％,明显高于对照组53．19％,差异有统计学意义（P〈0．05）;观察组控制出血时间和完全止血时间均低于对照组,差异有统计学意义（P〈0．05）。治疗后观察组FSH水平明显下降,与对照组和本组治疗前比较,差异有统计学意义（P〈0．05）;而LH、E：水平与治疗前比较,差异无统计学意义（P〉0．05）。对照组治疗前后FSH、LH和E,的水平比较,差异无统计学意义（P〉0．05）。对照组不良反应率高于观察组,差异有统计学意义（P〈0．05）。结论去氧孕烯炔雌醇在围绝经期功血患者止血中安全有效,值得临床应用。     

Multicenter study of the efficacy,cycle control and tolerability of a phasic desogestrel-containing oral contraceptive

Objective To investigate the efficacy, cycle control and tolerability of a phasic oral contraceptive containing ethinylestradiol 35/30/30 μg and desogestrel 50/100/150 μg.

Methods A multicenter study was conducted involving 2070 healthy, fertile women, who received study treatment for six treatment cycles.

Results Most of the participants (79%) had previously been using an alternative oral contraceptive. In 10 408 treatment cycles, two women became pregnant while on treatment (Pearl index, 0.25). The incidence of irregular bleeding was 10% before treatment, rising to 27% at cycle 1, and decreasing to 11% by cycle 6. Irregular bleeding was mainly due to spotting rather than breakthrough bleeding and the incidence of breakthrough bleeding remained below 2.2% for most of the study period. Only 1.8% of women withdrew due to bleeding irregularities. First-time oral contraceptive users initially experienced more irregular bleeding than switchers but these differences lessened over time. The most common adverse events during treatment were headache, breast tenderness and nausea. The incidence of these adverse events fell to below pretreatment levels with continued use.

Conclusion The phasic preparation was effective and well tolerated.     

A comparative study of the hemostatic effects of two monophasic oral contraceptives containing 30 μg ethinylestradiol and either 2 mg chlormadinone acetate or 150 μg desogestrel

Objectives To determine the effect of two low-dose monophasic oral contraceptives containing either 2 mg chlormadinone acetate or 150 μg desogestrel on blood clotting and fibrinolysis.

Methods In vivo markers of intravascular coagulatory and fibrinolytic activity were measured in 45 volunteers randomly assigned to a 6-month treatment with one of the two study preparations.

Results During oral contraceptive use, the procoagulatory activity increased (increased prothrombin fragment 1+2), the anticoagulatory capacity changed (increased protein C activity, decreased activated protein C sensitivity, decreased protein S activity and decreased antithrombin III activity) and the fibrinolytic system was activated (increased concentrations of plasmin-antiplasmin complexes and d-dimer as well as total fibrin degradation products). There were no relevant differences between the two medication groups.

Conclusion Our results demonstrate that both oral contraceptive preparations have comparable effects on the hemostatic system. There was a shift towards a new equilibrium of hemostatic activities, both coagulatory and fibrinolytic, at a higher turnover rate. Changes did not exceed the range of normal variation and were comparable to the published effects of other low-dose oral contraceptives. There was no evidence of a differential risk of deep vein thrombosis between the two preparations.     

Third- and second-generation oral contraceptives are associated with similar risk estimates for venous thromboembolism

A scientific discussion between 1995 and 1999 addressed the question whether second- and third-generation oral contraceptives (OCs) were associated with different risks of venous thromboembolism (VTE). Results from three epidemiological studies became available in the course of 1995, in which such differences were observed. Although it was unclear at that time whether these observations reflected causality or were induced by bias and/or confounding, some regulatory bodies in Europe restricted the indication for use of third-generation oral contraceptives. Immediate media attention generated a pill scare in those, but also other, countries.

Indications for the influence of bias were observed in the initial studies of 1995 and further substantiated in subsequent utilization and prescribing surveys. The most important bias seemed to be related to differences in age and duration of use between third- and second-generation OC users. A number of new studies as well as new analyses in two of the 1995 databases included measures to limit the effect of the identified biases/confounders. These studies observed similar risks of venous thromboembolism with second- and third-generation oral contraceptives. Two other recently published studies did not or could not include the same level of control for confounding and reported similar results as the 1995 studies, thus reconfirming the relevance of the identified confounders. Population data show that the massive switch in the UK from third-generation OCs to second-generation OCs in 1995 has not resulted in a reduction of the incidence of VTE in OC users after 1995, illustrating that the risk of VTE is not determined by the type of low-dose pill used. In addition, data from trend analyses, spontaneous reporting and studies addressing hemostatic mechanisms in pill-users also do not support a potential difference in risk of VTE between users of second- and third-generation OCs.     

妇科止血灵胶囊联合去氧孕烯炔雌醇治疗功能失调性子宫出血的疗效观察

目的 探讨妇科止血灵胶囊联合去氧孕烯炔雌醇片治疗功能失调性子宫出血的临床疗效。方法 选取2022年6月—2023年8月佳木斯市妇幼保健院收治的104例功能失调性子宫出血患者,按照随机数表法将104例功能失调性子宫出血患者分为对照组（52例）和治疗组（52例）。对照组口服去氧孕烯炔雌醇片,于月经周期第5天开始,初始剂量为1片/次,2次/d,连用3 d后改为1片/次,1次/d,连续治疗3周。治疗组患者在对照组治疗基础上口服妇科止血灵胶囊,4粒/次,3次/d。两组均连续治疗3周。观察两组的临床疗效和中医症候改善时间,比较两组治疗前后子宫内膜厚度、血红蛋白、激素指标的变化情况。结果 治疗后,治疗组患者的总有效率为94.23%,显著高于对照组80.77%（P＜0.05）。治疗后,两组子宫内膜厚度降低,而血红蛋白水平升高（P＜0.05）;与对照组比较,治疗后治疗组子宫内膜厚度减小,而血红蛋白水平更高（P＜0.05）。与对照组比较,治疗组腰膝酸软、面色晦黯、小便频数改善时间更短（P＜0.05）。与治疗前比较,治疗后两组雌二醇、促卵泡激素、孕酮水平均显著降低（P＜0.05）;与对照组比较,治疗后治疗组患者雌二醇、促卵泡激素、孕酮水平更低（P＜0.05）。结论 妇科止血灵胶囊联合去氧孕烯炔雌醇治疗功能失调性子宫出血可获得较好的治疗效果,能有效改善患者的中医症状,降低子宫内膜厚度、提高血红蛋白水平,改善机体激素紊乱的状态,且不良反应少。     

孕三烯酮治疗子宫内膜异位症效果及不良反应的Meta分析

目的：对比分析孕三烯酮在药物治疗子宫内膜异位症（EMs）中的价值。方法：系统检索OVID、MEDLINE、CNKI数据库获得随机对照试验,按Cochrane系统评价方法进行Meta分析。结果：孕三烯酮的症状缓解率优于妈富隆（RR=8.270,95%CI：1.046~65.384）,弱于促性腺激素释放激素激动剂（GnRHa）（RR=0.888,95%CI：0.845～0.933）,与达那唑（RR=1.043,95%CI：0.949~1.146）、米非司酮（RR=0.972,95%CI：0.943~1.003）及中药治疗（RR=0.954,95%CI：0.905~1.006）相比差异无统计学意义。在用药后累计妊娠率的改善方面孕三烯酮弱于GnRHa（RR=0.792,95%CI：0.657～0.954）,与米非司酮相比差异无统计学意义（RR=0.913,95%CI：0.730~1.140）。孕三烯酮的不良反应发生率（肝损伤）高于米非司酮（RR=1.865,95%CI：1.453~2.394）和妈富隆（RR=8.270,95%CI：1.046~65.384）,与GnRHa相比总体发生率差异无统计学意义（RR=1.308,95%CI：0.965～1.772）,但相应表现有所不同。2种剂量的孕三烯酮对EMs患者的美国生殖医学协会EMs分期（AFS评分）的改善差异无统计学意义（SMD=0.185,95%CI：-0.491~0.861）。结论：孕三烯酮作为治疗EMs的二线药物,总体效果弱于GnRHa,增加剂量对疗效无明显改善。在不良反应可接受的范围内,是可选药物之一。     

Effects of two different oral contraceptives on homocysteine metabolism in women with polycystic ovary syndrome

PURPOSE: This study was conducted to evaluate the effects of two different oral contraceptives (OCs) on homocysteine (Hcy) metabolism in 20 women with polycystic ovary syndrome (PCOS). METHODS: Women were randomly allocated to receive either the biphasic OC containing 40/30 mug ethynylestradiol (EE)+25/125 mug desogestrel (DSG; n=10) or the monophasic OC containing 35 mug EE and 2 mg cyproterone acetate (CPA; n=10). Investigations were performed before and after 6 months of treatment. Fasting vitamin B(12), folate, Hcy and insulin sensitivity (SI), and glucose utilization independent of insulin (Sg), by the minimal model method, were evaluated. RESULTS: Folate and vitamin B(12) were not significantly modified by either OC. EE/DSG decreased SI (2.53+/-0.35 vs. 1.68+/-0.45; p<.05), without modifying Hcy (9.54+/-0.7 micromol/L vs. 9.18+/-0.6 micromol/L). EE/CPA improved SI (1.47+/-0.38 vs. 3.27+/-0.48; p<.04) and decreased Hcy (9.8+/-1.9 micromol/L vs. 7.9+/-0.9 micromol/L; p<.05). This study indicates that in women with PCOS, EE/CPA, but not EE/DSG, improves IS and decreases fasting Hcy.