缓释左旋-18甲基炔诺酮皮埋避孕剂

时采用NorplantR埋植剂和仿制Norplant的国产埋植剂I型避孕的育龄妇女骨密度和骨代谢改变进行了1年的随机前瞻性临床观察.61例正常妇女被分为两组Norplant埋植剂组30例,国产埋植剂组31例.两组于埋植前和埋植后第12个月时采用双能X线骨密度测定仪(DEXA)分别测定了腰椎L2～L4、股骨近端骨密度和骨矿含量.两组妇女埋植后第12个月时腰椎L2～L4骨密度和骨矿含量均较埋植前明显增加(P＜0.01),Norplant组骨密度平均增加2.40%,骨矿含量平均增加3.34%,国产埋植剂组分别增加2.75%和4.47%;从年龄分析,以25～29岁组腰椎L2～L4骨密度埋植后增加最为显著,Norplant组P＜0.05,国产埋植剂组P＜0.01.国产埋植剂组妇女埋植后第12个月时股骨大粗隆骨密度和骨矿含量较埋植前明显增加(P＜0.01);国产埋植剂组妇女空腹尿羟脯氨酸/肌酐比值埋植后第12个月时较埋植前明显下降(P＜0.01);对使用妇女腰椎、股骨骨密度和骨代谢生化指标的影响,在两种埋植剂之间埋植前后比较均无显著差别(P＞0.05).左旋-18甲基炔诺酮皮埋避孕剂对绝经妇女的骨骼是非有害的,对年轻妇女骨峰值的获得无明显影响.     

孕酮对田鼠子宫的作用:快速抑制~3H-雌二醇的核保留

17β-雌二醇(E_2)和孕酮(P)相互作用调节着哺乳类子宫结构和机能的周期性变化。近年来有些学者通过观察受体的激素调节,对子宫内E_2和P交互作用的分子基础进行了研究,他们发现,E_2可以刺激E_2和P胞浆受体的合成,而P拮抗雌激素的作用,其机理可能是由于P抑制E_2胞浆受体的合成(或补充)。本实验观察了在体条件下P对田鼠子宫的核部分和胞浆部分摄取和保留~3H-E_2的作用,同时用小肠作为对照组织。成年雌性田鼠,于动情间期切除卵巢,皮下埋植E_2以维持循环中E_2处于较高的生理浓度。24小时后除去埋植的E_2,或皮下注射~3H-E_2同时皮下注射P。或皮下注射~3H-E_2同时注射玉米油。注药后     

使用国产长效避孕皮下埋植剂妇女五年内血清雌二醇、孕酮、左旋18甲基炔诺酮水平

５例使用国产长效避孕皮埋剂（Ｓｉｎｏ－Ｉｍｐｌａｎｔ，以下简称为Ｓｉｎｏ）长达五年以上的妇女，每年末抽血一个周期（即连续４～５周，每周定时抽血一次）。用ＲＩＡ测定血清中雌二醇（Ｅ２），孕酮（Ｐ）和左旋１８甲基炔诺酮（ＬＮＧ）水平。研究结果显示：长期使用Ｓｉｎｏ未出现相似的卵巢内分泌反应。８４％（２１／２５）抽血周期血清Ｅ２水平出现峰值（Ｅ２＞１５０ｐｇ／ｍｌ），以例数计，埋植后１～４年内每年有８０％（４／５）抽血周期血清中Ｅ２显示峰值，第五年为１００％（５／５）。４０％（１０／２５）抽血周期显示黄体活性（Ｐ＞３ｎｇ／ｍｌ），以例数计，埋植第一年为０％（０／５）；第二年为４０％（２／５）；３～５年每年６０％（３／５）表现黄体活性。５例对象中有２例埋植后五年内未见血清Ｐ＞１ｎｇ／ｍｌ，而且这２例分别在埋植后１～２年及３～４年未见Ｅ２峰（Ｅ２＜１５０ｐｇ／ｍｌ）。５例对象埋植前对照周期均有正常的Ｅ２峰和黄体活性。在用Ｓｉｎｏ的５年内抽血周期血清Ｅ２和Ｐ的均值都低于对照周期。在用Ｓｉｎｏ期间，有黄体活性的周期均伴有Ｅ２峰。然而，并非所有有Ｅ２峰的周期都表现黄体活性。在埋植第一年，除第一个月外，血清ＬＮＧ水平低而相对?     

缓释左旋-18甲基炔诺酮皮埋避孕剂对骨密度和骨代谢的影响

对采用 Norplant R埋植剂和仿制 Norplant的国产埋植剂 型避孕的育龄妇女骨密度和骨代谢改变进行了 1年的随机前瞻性临床观察。 6 1例正常妇女被分为两组 :Norplant埋植剂组 30例 ,国产埋植剂组 31例。两组于埋植前和埋植后第 12个月时采用双能 X线骨密度测定仪 (DEXA)分别测定了腰椎 L2 ～ L4、股骨近端骨密度和骨矿含量。两组妇女埋植后第 12个月时腰椎 L2 ～ L4骨密度和骨矿含量均较埋植前明显增加 (P<0 .0 1) ,Norplant组骨密度平均增加2 .40 % ,骨矿含量平均增加 3.34 % ,国产埋植剂组分别增加 2 .75 %和 4.47% ;从年龄分析 ,以 2 5～ 2 9岁组腰椎 L2 ～ L4骨密度埋植后增加最为显著 ,Norplant组 P<0 .0 5 ,国产埋植剂组 P<0 .0 1。国产埋植剂组妇女埋植后第 12个月时股骨大粗隆骨密度和骨矿含量较埋植前明显增加 (P<0 .0 1) ;国产埋植剂组妇女空腹尿羟脯氨酸 /肌酐比值埋植后第 12个月时较埋植前明显下降 (P<0 .0 1) ;对使用妇女腰椎、股骨骨密度和骨代谢生化指标的影响 ,在两种埋植剂之间埋植前后比较均无显著差别 (P>0 .0 5 )。左旋 - 18甲基炔诺酮皮埋避孕剂对绝经妇女的骨骼是非有害的 ,对年轻妇女骨峰值的获得无明显影响。     

国产两根型皮埋剂配伍十一酸睾酮(TU)对中国男子垂体-性腺轴的影响

目的 :观察国产两根型皮埋剂 Sino-implant及十一酸睾酮 (TU)针剂联合应用对中国男性垂体促性腺激素和睾酮水平的影响。方法 :共征集自愿对象 1 6名 ,前臂埋植 Sino-im-plant,每根含左旋 1 8-甲基炔诺酮 75mg,并于 3周后每月肌注针剂十一酸睾酮 (TU) ,(2 50 mg) ,共 3次。结果 :放置皮埋剂后血清中 FSH、L H水平有所下降。注射第 1针 TU后 ,FSH、L H水平进一步下降 ,于注射后 1周达到谷值 ,之后 FSH、L H水平又有所上升 ;注射第 2、3针 TU后 ,FSH、L H水平变化情况与第 1针时相似。此外 ,皮埋后对象血清睾酮水平也有所下降 ,注射第 1针 TU后 ,则睾酮水平升高 ,并于注射后 1周达峰值 ,之后睾酮水平又有所下降 ;注射第 2、3针 TU后血清睾酮水平变化情况与第 1针时相似。结论 :皮埋剂Sino-implant和 TU配伍应用可对垂体促性腺激素分泌产生协同抑制作用 ,从而使内源性睾酮水平下降 ;但注射 TU可补充睾酮 ,使之维持正常水平。故国产皮埋剂配伍 TU很有希望用于男性避孕     

引产和引产前血清孕酮、雌二醇和雌三醇的水平

本文研究血清孕酮(P)、雌二醇(E_2)和雌三醇(E_3)水平与规律宫缩发动的关系。由于对宫缩自然发动与激素变化浓度关系的监视非常困难,因而测定人工引产前后血清P、E_2及E_3的水平。 83例孕37周或以上的单胎活婴,低位破水继之静脉点滴催产素,引产后临产2小时的产妇作为本文研究对象。引产指征:过期妊娠(预产期超过10     

舌下含化雌激素治疗产后抑郁症

报道2例完全符合I(CD)-10产后抑郁症标准,并经舌下含化17-β雌二醇(E_2)治疗痊愈的病例。 例1 女性,30岁,无精神病病史,夫妻关系稳定。第一胎产后第2周,出现焦虑和睡眠障碍。随后数周,有忧郁、精神紧张、易怒、失眠、食欲减退。给予其奥沙西泮15～30mg,并予以心理咨询,仅暂时见效。分娩2月后,症状加剧,几乎达错乱程度,于是入院治疗。确诊为产后严重性抑郁症(MADRS总积分43)。测定血清E_2水平为140pmol/L,但其它血液检测(包括甲状腺功能)均正常。经患者同     

依托孕烯植入剂治疗痛经的疗效及安全性分析

目的:探讨依托孕烯植入剂治疗痛经的疗效及安全性。方法:选择2013年9月至2016年4月在我院埋植依托孕烯植入剂治疗痛经的患者。依托孕烯植入剂植入术后3月、半年、1年进行随访。比较患者术前及术后痛经情况、月经模式、肝肾功能;对子宫腺肌病患者还需比较子宫大小及CA125水平。结果:共73例患者纳入研究,66例术前有中重度痛经,术后3月中、重度痛经者仅10例,占13.7%(χ2=95.312,P=0.000),31例痛经完全消失;3月后痛经情况进一步改善,但与3月比较差异无统计学意义(P0.05)。对于子宫腺肌病患者,术后子宫大小无明显变化(P0.05),术后血清CA125水平显著下降(P0.05)。术后31例(42.5%)患者出现点滴状阴道流血。术后无严重副反应。结论:皮下埋植依托孕烯植入剂是治疗痛经效果确切、较为安全的方法。     

皮下埋植剂Implanon和Norplant的临床对比性研究

目的　比较皮下埋植剂Implanon(Implanon)和皮下埋植剂Norplant(Norplant)避孕的有效性、可接受性和阴道出血的情况。方法　采用随机对照的前瞻性研究方法 ,将 10 0例健康妇女 ,分为两组 ,使用Implanon 75例 (Implanon组 ) ,使用 2 5 5 5妇女年 ;使用Norplant 2 5例 (Norplant组 ) ,使用 94 4妇女年 ,共随访 4年 ,进行临床比较性研究。结果　两组均无妊娠发生。以 90d为 1个参照时限 ,Implanon组的阴道出血 (出血或滴血 )天数 ,由第 1个参照时限平均 33d ,减少至第 16个参照时限的 2 1d ;Norplant组由平均 31d减少至 2 0d。平均每个参照时限的出血次数 ,Implanon组为 2 2 5次 ,Norplant组为 2 99次 (P <0 0 5 )。有 1次或 1次以上出血和 (或 )滴血≥ 10d的发生率 ,Implanon组由第 1个参照时限的 6 6 %下降至第 16个参照时限的 2 7% ;Norplant组由 6 9%下降至 2 2 %。Implanon组有 7例 (9% )因出血过多或出血时间过长停止使用埋植剂。Norplant组有 1例 (4% )因使用埋植剂后闭经 2年而停止使用埋植剂。平均埋入埋植剂所用时间 ,Implanon组为 11s,Norplant组为 10 3s(P <0 0 0 1) ;平均取出埋植剂所用时间 ,Implanon组为 2 7s ,Norplant组为 10 2s(P <0 0 0 1)。结论　两种皮下埋植剂避孕有效性高、     

腹腔镜单侧卵巢子宫内膜异位囊肿剥除术对血清抗苗勒管激素水平变化的影响

目的:探讨腹腔镜下单侧卵巢子宫内膜异位囊肿剥除术对血清抗苗勒管激素(AMH)变化的影响。方法:测定128例单侧卵巢囊肿患者手术前及术后1周、3个月及6个月的AMH、FSH及E_2水平,并进行窦卵泡计数。结果:术后1周,AMH、FSH及E_2均发生改变,且差异有统计学意义(P0.05);术后3个月,血FSH和E_2水平已恢复正常,窦卵泡计数与术前无明显改变(P0.05),但AMH水平仍低于术前(P0.05);术后第6个月,AMH水平仍低于术前水平(P0.05),而FSH、E_2及窦卵泡数均较术前比较,差异无统计学意义(P0.05)。年龄35岁患者的术后AMH下降率显著高于年龄≤35岁者(P=0.001)。结论:单侧囊肿卵巢囊肿术后半年卵巢储备功能仍处于恢复阶段,AMH可作为敏感的卵巢储备标志物,优于基础FSH测定及窦卵泡计数。     

长期使用Norplant皮下埋植剂妇女血清左炔诺孕酮水平的测定

目的（１）测定ｏｒｐｌａｎｔ皮下埋植剂（１－１１年）的妇女血清左诺孕酮水平,预测其可能使用的最长有效期限;（２）观察长期（５年）用药后血清ＬＮＧ水平与受试者体重间相关性。方法 应用放射地测定血清中ＬＮＧ水平。结果 使用Ｎｏｒｐｌａｎｔ１、３、５年后,血清ＬＮＧ均值分别为１２７３．５μｍｏｌ／Ｌ、９２４．０ｐｍｏｌ／Ｌ和７３９．６ｐｍｏｌ／Ｌ。第５－７年血清ＬＮＧ均呈线性降低,第７－１０年,血清ＬＮ     

新型左炔诺孕酮/炔雌醇复方避孕贴剂的家兔药代动力学研究

目的:探讨新型左炔诺孕酮(levonorgestrel,LNG)和炔雌醇(ethynylestradiol,EE)在家兔体内的药物动力学特征,评价多次给药后是否出现药物蓄积情况。方法:家兔在单次和多次给药及停止给药后不同时间点耳缘静脉采血,选择放射免疫分析(radioimmunoassay,RIA)法测定各时间点各组家兔雌/孕激素的血药浓度,使用药物动力学软件计算各药物动力学参数并对其进行统计分析。结果:单次给药后受试贴剂低(10cm2)、中(20 cm2)和高剂量(40 cm2)组血清LNG峰浓度(Cmax)分别为1.04±0.12 ng/ml、2.42±0.60 ng/ml和4.90±1.39 ng/ml,3组间有显著差异(P<0.05)。血药浓度-时间曲线下面积(AUC)分别为49.93±9.79h.ng/ml、115.14±34.25 h.ng/ml和251.22±80.55 h.ng/ml,3组间有显著差异(P<0.01);血清EE峰浓度(Cmax)分别为112.00±45.50 pg/ml、139.23±28.23 pg/ml和290.26±66.62 pg/ml,中、高剂量组间有显著差异(P<0.05),而中、低剂量组间无统计学差异(P>0.05)。EE血药浓度-时间曲线下面积(AUC)分别为4.70±1.34 h.ng/ml、6.59±1.23h.ng/ml和16.59±2.33 h.ng/ml,中、高剂量组之间有显著差异(P<0.01)。Evra参比避孕贴剂组血清LNG浓度的Cmax为3.16±1.00 ng/ml,AUC为155.29±46.14 h.ng/ml,与LNG/EE避孕贴剂中剂量组(拟采用的临床试验剂量)相比,两者无显著差异(P>0.05)。中剂量组血清EE浓度与Evra避孕贴剂的相比显著降低(P<0.05)。多次给药后LNG/EE避孕贴剂10 cm2组和20 cm2组在重复给药10次的过程中未出现LNG和EE血药浓度蓄积现象,Evra贴剂组在重复给药4次的过程中未出现LNG和EE血药浓度蓄积现象。结论:中剂量的LNG/EE避孕贴剂具有良好的避孕效果,同时其副作用可能小于Evra。     

A pharmacokinetic study with a low-dose oral contraceptive containing 20 microg ethinylestradiol plus 100 microg levonorgestrel.

This study investigated the pharmacokinetics of a dose-reduced oral contraceptive containing 20 microg ethinylestradiol (EE) + 100 microg levonorgestrel (LNG) in 18 young, healthy females. Serum levels of EE and LNG were determined after single and repeated daily oral administration over three treatment cycles, each consisting of 21 treatment days followed by a 7-day treatment-free period. Additionally, the time courses of sex hormone-binding globulin (SHBG), corticoid-binding globulin (CBG) and total and free testosterone serum levels were analyzed. Both active ingredients were rapidly absorbed and maximum concentrations in serum were reached between, on average, 1 and 2 h after single and multiple administrations, respectively. Concentrations of EE increased during repeated daily administration. An approximate two-fold accumulation was calculated based on the comparison of EE area under the curve (AUC) (0-24 h) values determined after the first and the last tablet administration within a treatment cycle. LNG serum concentrations also increased during repeated daily administration, reaching steady-state levels after about 11 days. Based on the comparison of AUC (0-24 h) values determined after the first and the last tablet administration, LNG accumulated approximately by a factor of 3 within a treatment cycle. Steady-state pharmacokinetics of LNG were similar at the end of the first and the third treatment cycles, indicating no further accumulation of LNG beyond a treatment cycle under long-term use of this combined oral contraceptive. The clearance and volume of distribution of LNG decreased and the terminal half-life increased after repeated daily administration, compared with single administration. These effects have also been reported for other LNG/EE combinations. SHBG serum concentrations increased during repeated daily intake by, on average, 1.5-1.6-fold, and for CBG, an average increase of 1.4-1.8-fold was found. Although free testosterone concentrations declined during repeated daily administration by about 40%, total testosterone remained relatively unchanged at a low level. In conclusion, the pharmacokinetics of EE and LNG determined in the present study were in good agreement with those previously reported for 30 microg EE + 150 microg LNG, taking the 33% dose reduction into account.     

长效孕激素炔诺酮庚酸酯及复方18甲基炔诺酮对血清性激素结合球蛋白的影响

24例妇女肌注炔诺酮庚酸酯200 mg,肌注前血清性激素结合球蛋白(SHBG)为53.32±23.23 nmol╱L。注射后5天为41.99±17.06nmol/L(P<0.05),21天降至最低值14.72±10.01 nmol/L,以后逐渐回升,直至注射后84天仍未回复到原来水平(34.46±20.39 nmol/L)。10例妇女单次口服18甲基炔诺酮6 mg+炔雌醚3 mg,服药前血清SHBG水平为42.76±13.89 n mol/L,服药后7天为62.53±10.90 nmol/L(P<0.01),14天达峰值为71.33±5.77 nmol/L,以后持续此高水平,直至服药后56天;8例连续3次口服18甲+炔雌醚,每次间隔23天,服药前血清SHBG水平为44.94±15.36 nmol/L,第1次服药后9天为83.46±10.08 nmol/L(P<0.01),16天达峰值为91.74±2.28nmol/L,以后持续高水平直至第3次服药后30天,第2、3次重复给药对业已升高的SHBG水平无影明显响。第2、3次服药后LNG峰值明显高于首次服药后峰值6倍。     

左旋18-甲基炔诺酮经阴道给药的药代动力学和药效学研究

本文比较了左旋18-甲基炔诺酮(LNG)制剂Postinor单剂量(0.75mg)口服和阴道给药的药代动力学,并研究了这种制剂经阴道多次给药的药代动力学及对卵巢功能的影响。征集6例月经规则的健康育龄妇女。第一周期,每例对象每次于阴道深处放置一片Postinor,共8次,每2次间隔为48小时;第二周期,每例对象口服一片相同的LNG制剂,放免测定血清LNG、雌二醇和孕酮水平。结果表明在第一周期,除1例对象在中期有一较高的雌二醇峰以外,其余雌、孕激素水平均呈明显低平状态;口服和阴道放置相同的单剂量LNG以后血清LNG浓度时间曲线分别符合二室与一室开放模型。由此提示与口服相比,Postinor经阴道给药后吸收缓慢,且血清LNG峰值低,而消除过程则两种给药途径较为相似;Postinor经阴道给药可明显抑制排卵。     

The effect of physical training on the pharmacokinetics of steroidal contraceptives]

In 8 female sports students (runners) aged 20 and 21 years and 10 women between 20 and 40 years of age, who regularly underwent body building training, serum levels of ethinylestradiol (EE2) and levonorgestrel (LNG) have been determined under conditions of exercise as well as in rest, prior to and following the intake of 1 tablet of Gravistat (0.05 mg EE2, 0.125 mg LNG). Blood samples were obtained at points 0, 2, 6 and 24 hours. Exercise (5000 meter running and intensive body building training of one hour duration, respectively) was started immediately after intake of the steroid combination. There were no significant differences in the serum concentration levels obtained during exercise and rest. But exercise consistently resulted in a slight decrease of EE2 and LNG serum concentrations and the area under curve values.     

Serum estradiol in women ingesting combination oral contraceptive steroids

A study of the effect of combination oral contraceptives upon endogenous ovarian estrogen production was done by measuring serum estradiol levels in 3 groups of women. The first group of 3 women gave daily serum samples during 1 control and 2 treated cycles (2 mg. norethindrone and 100 mu-g mestranol received daily for 20 days), and levels of follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were measured. A second group (6) taking oral contraceptives for at least a year were measured daily during 1 cycle for estradiol only. Each of 97 women in the third group, taking the pill from 1 to 6 years, gave a single blood sample taken at random during the cycle, to be assayed for estradiol. Estradiol levels in women receiving oral contraceptives were low, usually in the range of 20-30 pg./ml., similar to those found in the early follicular phase in ovulatory cycles, and significantly higher than levels found in postmenopausal women. Exogenous estrogen in the pill, together with this level of endogenous estradiol, should be sufficient to prevent any harmful effects associated with estrogen deficiency. The finding that estradiol levels remain low in the first cycle of therapy is consistent with previous studies which indicate that one of the mechanisms of action of hormonal contraceptives is a direct effect upon the ovary.     

Estradiol suppression and recovery during leuprolide acetate treatment in women as determined weekly by an ultrasensitive recombinant cell bioassay

We studied the timeframe of suppression and recovery of estradiol after injection with leuprolide acetate utilizing an ultrasensitive recombinant cell bioassay for estradiol in eight normal premenopausal women. Previous studies have shown suppression of gonadotropins and estradiol at 4 weeks after the depot injection, but no studies have shown the weekly time course of estradiol suppression or recovery. Four women received one 3.75 mg i.m. injection of leuprolide acetate and four received two 3.75 mg doses of leuprolide acetate 4 weeks apart. Estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured weekly for 8 to 12 weeks. Estradiol was significantly suppressed to 26.6 ± 19.3% of baseline values by week 3 after the initial dose of leuprolide acetate and suppressed to 2.7 ± 3.1% of baseline values by week 4 (p < 0.01 versus baseline). The actual values were less than 14.7 pmol/l (4 pg/ml) in all women by week 4. Estradiol remained suppressed for 8 weeks after one dose of leuprolide acetate and remained suppressed for 6 weeks after a second dose administered 4 weeks later. LH and FSH followed a similar pattern, but only remained suppressed for 7 weeks after one dose of leuprolide acetate and for 6 weeks after two doses. Estradiol levels at baseline were significantly correlated with body mass index (BMI). We also studied one postmenopausal woman. Her baseline estradiol levels were 10.3 pmol/l (2.8 pg/ml) and were suppressed to 3.9 pmol/l (1.1 pg/ml) by 2 weeks after leuprolide acetate.

In conclusion, estradiol was suppressed to postmenopausal levels by the end of the first month of reatment with leuprolide acetate, as determined by an ultrasensitive bioassay. Higher doses would need to be tested to determine whether greater suppression can be achieved. The hypothalamic–pituitary–gonadal axis begins to recover 7 weeks after one dose and 6 weeks after a second dose of leuprolide acetate. This confirms the adequacy of 4-week dosing to maintain estradiol and gonadotropin suppression in adult women treated with leuprolide acetate, but raises the question whether less frequent dosing may be possible in some situations, or whether higher doses may be needed in some situations for an even greater degree of estradiol suppression.