左炔诺孕酮口崩片的人体药代动力学及相对生物利用度研究

目的:比较左炔诺孕酮口崩片和市售口服片的人体药代动力学及相对生物利用度。方法:20名健康女性志愿者随机双交叉单剂量服用左炔诺孕酮口崩片和市售口服片,剂量均为0.75 mg,分别于服药前和服药后72 h内不同时间点抽取静脉血,清洗期为2周,以放射免疫分析(radioimmuno-assay,RIA)法测定血清中左炔诺孕酮的浓度,并利用SAS软件计算口崩片与市售口服片的药代动力学和相对生物利用度。结果:采用RIA测定左炔诺孕酮的最低检测限为10 pg/ml,低、中、高(300 pg/ml、2 000 pg/ml、6 000 pg/ml)3种浓度左炔诺孕酮标准质控血清的日内精密度分别为12.4%、9.3%、3.1%(n=5),日间精密度分别为4.3%、11.7%、5.7%(n=5)。口崩片和市售口服片的主要药代动力学参数分别为:tmax1.6±0.2 h、tmax1.7±0.3 h;Cmax6.2±0.8 ng/ml、Cmax6.5±1.0 ng/ml;AUC0～72 h 85.5±24.4 h.ng/ml、AUC0～72 h 90.8±27.1 h.ng/ml;AUC0-inf96.8±27.9 h.ng/ml、AUC0-inf 101.2±30.8 h.ng/ml;t1/2 25.3±3.5 h、t1/224.2±3.1 h。口崩片的AUC0～72 h、AUC0-inf和Cmax的90%置信区间分别为市售口服片相应参数的87.72%～101.87%、89.01%～103.73%和89.80%～101.75%。口崩片tmax与市售口服片相比无显著差异(P>0.05)。口崩片的相对生物利用度为96.1±18.3%。结论:建立的分析方法准确灵敏,可用于左炔诺孕酮血药浓度的测定;左炔诺孕酮口崩片与市售口服片的生物利用度无显著性差异,2种制剂具有生物等效性。     

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。     

经淋巴管灌注卡铂脂质体的药代动力学实验研究

目的 :研究卡铂脂质体 (CPL)经淋巴管内灌注 (ILVP)的体内药代动力学。方法 :随机将 6 0只雌性新西兰白兔分为 3组 :ILVP组 ,经兔窝淋巴结输出管穿刺置管给药 ;腹腔内注射 (IPI)组及静脉内注射 (IVI)组。每只给予CPL 30ml混悬液 ,存活 16 8h后处死。用石墨炉原子吸收分光光度法测定每组各时点的外周血及盆腔腹膜后淋巴结组织中铂总 (Pt)浓度 ,并摘取兔淋巴结及心、肝、脾、肾组织作病理学检查CPL的毒性作用。结果 :ILVP组淋巴结铂峰最大浓度 (Cmax)为 6 8.4 μg/g(湿重 ) ,药时曲线下面积 (AUC)为2 117.5 μg·h/g(湿重 ) ,外周血铂Cmax为 12 .8μg/ml,AUC为 2 10 .6 μg·h/ml ;IPI组淋巴结铂Camx为 35 .2 μg/g(湿重 ) ,AUC为 94 4 .2 μg·h/g(湿重 ) ,外周血铂Cmax为 11.4 μg/ml,AUC为 2 76 .3μg·h/ml;IVI组淋巴结铂Cmax为 18.4 μg/g(湿重 ) ,AUC为 319.9μg·h/g(湿重 ) ,外周血铂Cmax为 4 0 .7μg/ml,AUC为 6 6 8.0 μg·h/ml。各实验组间兔淋巴结铂浓度分布差异有显著性 (P <0 .0 5 )。其中ILVP组淋巴结铂Camx是IPI组的 1.9倍 (P =0 .0 4 ) ,是IVI组的 3.7倍 (P =0 .0 13)。外周血中铂浓度 :IVI组高于ILVP组 (P =0 .0 4 4 ) ,但IPI组与ILVP组差异无显著性 (P =0 .6 3)。淋巴结病理形态学检     

左旋18—甲基炔诺酮事后药的药物动力学及药效学研究

本研究为6例健康妇女,在月经周期排卵前后,口服左旋18-甲基炔诺酮(简称18-甲)0.75mg/天,连续七天的药物动力学和药效学。服药期间,每日在服药前取血,此外在第一和第七天服药后1,2,4,8,12和24小时取前臂静脉血,放射免疫法测定血中18-甲水平。药—时曲线表明所有受试者均为开放二室模型,药时方程为C(t)=Ae~(-αt)+Be~(-βt)-(A+B)e~(-kat)。第一天服药后药物动力学参数:达峰时间T_(max)3.74±1.06h,峰值C_(max)=8.91±2.25ng/ml,消除半寿期t_(1/2)β=11.98±2.99h,K_a=0.476±0.1202h,表观分布容积V_d=102.8±35.81L,体内总廊清率Cl=6.34±2.37L/h,血药浓度—时间曲线下面积Auc=136.91±50.58ng/ml/h;第七天药物动力学参数:T_(max)=3.46±1.12h,C_(max)=6.92±2.39ng/ml,t_(1/2)β=14.45±4.55h,K_a=0.4584±0.1640h,V_d=147.81±76.01L,Cl=6.95±4.21L/h,Auc=134.25±56.29ng/ml/h。比较服药第一天和第七天的药物动力学参数经(?)t-test 计算,两者之间无统计学差异。服药期间,每日血标本用RIA法测定雌二醇E_2,孕酮P,促黄体生长激素LH,促卵泡激素FSH,和促泌乳激素PRL。结果发现血内FSH 水平明显偏低,6例中4例LH 峰偏低或消失;有两例孕酮峰消失;E_2及PRL 的变化较小,其值在正常范围内。     

肺表面活性物质羊膜腔注射预防早产儿呼吸窘迫综合征的疗效及药物浓度分析

目的:探讨肺表面活性物质(PS)羊膜腔注射预防早产儿呼吸窘迫综合征(NRDS)的药代动力学机制及疗效。方法:(1)药代动力学研究。实验动物为妊娠25天的兔胎。将0.1ml PS注入羊膜腔内,分别于1h、2h、4h(Ⅰ组、Ⅱ组、Ⅲ组)娩出兔胎并处死;气管内给药PS 0.1ml或生理盐水0.1ml(Ⅳ组、对照组)后1h,娩出兔胎并处死。各组留取兔胎末端肺组织检测DPPC浓度。(2)临床研究:妊娠28～32周胎肺不成熟早产病例。随机分为3组:PS羊膜腔给药组,分娩前将固尔苏1支注入羊膜腔内;PS气管内给药组,新生儿娩出后立即将固尔苏1支经气管插管注入支气管内;对照组,出生前后不予PS预防性给药。结果:(1)药代动力学:Ⅰ组与Ⅳ组比较,兔胎肺组织中DPPC含量无明显差异[(1.133±0.402)mg/g肺组织vs(1.170±0.145)mg/g肺组织,P>0.05],两组均明显高于对照组[(0.684±0.158)mg/g肺组织,P均<0.01]。Ⅱ组、Ⅲ组兔胎肺组织中DPPC含量较Ⅰ组明显下降,与对照组的差异无统计学意义(P>0.05)。(2)临床研究:3组新生儿孕龄、出生体重无明显差异。PS羊膜腔给药组及PS气管内给药组新生儿NRDS发生率无明显差异(13.3%vs 14.3%,P>0.05),显著低于对照组(35%)(P均<0.05);两组持续正压通气的频率无明显差异(16.6%vs 22.8%,P>0.05),均显著低于对照组(57.5%)(P均<0.05)。新生儿住院时间PS羊膜腔给药组为(27.8±9.6)天,PS气管内给药组为(26.8±11.7)天,均显著短于对照组[(33.7±11.8)天](P均<0.05)。PS羊膜腔给药组及气管内给药组新生儿均存活,对照组死亡4例。结论:PS羊膜腔给药可显著降低早产儿NRDS发生率并改善预后,可取得和气管内给药一样的效果,临床应用风险小,操作简单,值得临床推广应用。     

IVF-ET后黄体支持作用的评估

目的:研究IVF超排卵周期中,胚胎移植(ET)后是否需要黄体支持。方法:随机收集2001.12-2004.12时间本中心的237例23-39岁的不孕症妇女,其中60例自然排卵者为A组,177例采用GnRha长方案降调节超卵排,取卵后,因各种原因未进行移植者35例为B组;胚胎移植后4周B超确认宫内妊娠者随机分为C组(82例,采用短期黄体支持,自移植日起使用黄体酮80mg/d至移植后4周,即孕6周)和D组(60例,采用长期黄体支持,自移植日起使用黄体酮80mg/d至孕12周),比较A、B组妇女的黄体功能状况,C、D组的早期流产率。结果:B组月经来潮时间为取卵后11.5±0.5d,明显短于A组(排卵后13.9±1.4d),P<0.05,有统计学差异。B组黄体晚期(取卵后11d)孕酮水平下降明显,与黄体早期(取卵后2d)相比,比值为0.08±0.01,而A组黄体晚期的孕酮水平呈上升趋势,与黄体早期的比值为1.70±0.27,二组的比值差异非常显著(P<0.01)。C组早期流产率为7.3%,D组为6.7%,二者相比无统计学差异(P>0.05)。结论:①GnRha长方案降调节影响黄体功能。②移植后4周(孕6周)停用黄体酮并不增加流产率。     

米索前列醇用于足月妊娠引产不同给药途径的临床观察

目的为了观察米索前列醇(Misoprostol,米索)用于足月妊娠引产不同给药途径(舌下含服及阴道后穹窿给药)的临床效果.方法选择有引产指征,无引产及米索使用禁忌症的单胎、头位的足月妊娠妇女72例,随机分为A组(舌下含服组)、B组(阴道后穹窿组),分别用米索50μg舌下含服及阴道后穹窿给药,间隔4～6h重复给药,24h内最大剂量为200μg.结果两组的引产成功率分别为95%和93.7%.首次用药至规律宫缩开始时间分别为3.82±1.21h和3.45±1.42h,首次用药至胎儿娩出时间分别为8.60±4.42和8.82±4.87h.两组比较,差异无显著性(P＞0.05).但产后白细胞总数升高B组明显高于A组(P＜0.05).结论采用米索前列醇50μg含服给药法引产,方法更为简便、易行,更为安全有效.     

低剂量长、短效达菲林在控制性超促排卵中的疗效比较

目的:探讨低剂量长、短效达菲林在控制性超促排卵中的垂体降调效果及临床结局。方法:选择IVF-ET患者206例,均于前一月经周期黄体中期开始注射达菲林。随机分为3组,A组:n=100,长效达菲林1.25 mg;B组:n=56例,注射短效达菲林0.05 mg/d,至hCG日;C组:n=50,注射短效达菲林0.1 mg/d,至Gn日改为0.1 mg/次,qod至hCG日。结果:①Gn使用天数及用量:A组(11.6±2.5 d,2591.2±287.2 IU)显著多于B组(10.1±2.6 d,2198.6±383.4 IU)和C组(10.4±2.2 d,2 156±306.4 IU)(P<0.05)。②降调后Gn启动日血清LH值:A组为1.23±0.25 IU/L,B组为2.9±0.37 IU/L,C组为2.39±0.54 IU/L,A组显著低于C组,C组显著低于B组(P均<0.01)。③hCG注射日LH值:A组(1.48±0.12 IU/L)显著低于B组(2.50±0.34 IU/L)和C组(2.90±0.90 IU/L)(P<0.01)。④获卵数、成熟卵子数、优质胚胎数及临床妊娠率A组均明显高于B组和C组(P<0.01)。结论:长效达菲林1.25 mg垂体降调效果及临床结局均优于短效达菲林组。     

复方米非司酮联用加味八珍益母膏终止早孕的临床观察

目的:探讨复方米非司酮联用加味八珍益母膏终止早期妊娠的临床疗效。方法:早孕妇女共360例,随机分成西医治疗组(A组):复方米非司酮(米非司酮30mg+双炔失碳酯5mg)晨1片/d×2d,并于首次服药后48h加服米索前列醇600μg;中西医结合治疗组(B组):西药服用同A组,同时于服复方米非司酮和米索前列醇2h后开始口服加味八珍益母膏25g/次,bid×9d,观察分析其流产临床效果、孕囊排出时间、流产后阴道出血时间及服药后的不良反应,并随访转经情况。结果:B组完全流产率为97.2%,A组为91.1%;孕囊自行排出时间B组为3.1±1.4h,A组为3.7±1.7h;出血时间分别为11.4±3.8d和12.5±4.3d;转经时间分别为35.9±2.9d和38.7±3.3d,组间比较均有显著差异(P<0.01);服药后不良反应B组明显减轻。结论:复方米非司酮联用加味八珍益母膏可加速孕囊排出,提高完全流产率,缩短阴道出血时间,减少出血量,且明显减轻副作用,值得临床推广应用。     

Progesterone administration by nasal spray in menopausal women: comparison between two different spray formulations.

The aim of the study was to compare the bioavailability of progesterone dissolved in almond oil or dimethicone, and administered by nasal spray. Twenty healthy menopausal women were randomly allocated to treatment by four doses of intranasal spray either of a progesterone solution in almond oil, 2 mg/0.1 ml, corresponding to a total dose of approximately 11 mg of progesterone, or a progesterone solution in dimethicone 5 mg/0.1 ml corresponding to a total dose of approximately 28 mg of progesterone. Circulating progesterone levels were calculated at various time intervals following administration. The formulation with almond oil yielded a maximum progesterone concentration (Cmax of 3.75 ng/ml at Tmax = 60 min, and the area under the curve (AUC0-720) value was 1481.6 +/- 343. The formulation with dimethicone yielded a mean Cmax of 1.049 ng/ml at Tmax = 30 min; the AUC0-720 value was 302.06 +/- 37.5. Therefore, bioavailability of progesterone dissolved in almond oil proved to be largely superior compared to the solution in dimethicone. The crucial role of the carrier in the spray formulations is discussed; in addition to ensuring clinical safety, it must have good solubility for progesterone, be fluid enough to enable efficient 'spraying' and also must allow progesterone to be absorbed through the nasal mucosa.     

Clinical pharmacokinetic study of Org5187 as a low-dose oral contraceptive]

The pharmacokinetics of 3-keto-desogestrel and ethinyl estradiol (EE) and the safety of Org5187 (150 mcg desogestrel and 30 mcg EE) in 17 healthy Japanese women (single dose--8, multiple dose--9) were studied after oral administration. After single dose administration, Tmax, Cmax elimination 1/2 life (t1/2beta), and the area under the curve (AUC) of 3-keto-desogestrel were 1.8 +or- 0, 7 hour; 3.9 +or- 1.36 pmol/ml, 19.1 +or- 13.0 hours; and 28.6 +or- 22.9 pmol h/ml, respectively. On the other hand, those after multiple dose were 1.2 +or- 0.6 hour (Tmax), 12.12 +or- 5.49 pmol/ml (Cmax), 22.0 +or- 9.6 hour (t1/2beta), and 97.2 +or- 36.8 pmol h/ml (AUC), respectively. Pharmacokinetic parameters of EE were 1.69 +or- ), 96 hour (Tmax), 0.638 +or-0.025 pmol/ml (Cmax), 20.0 +or- 12.3 hour (t1/2beta), and 7.0 +or- 4.12 pmol h/ml (AUC) after single dose, and 1.11 +or- 0.5 (Tmax), 1.180 +or- 0, 315 pmol/ml (Cmax), 23.7 +or- 8.8 hour (t1/2beta), 11.7 +or- 3, 3pmol h/ml (AUC) after multiple dose. The serum concentrations of 3-keto-desogestrel and EE reached a steady state on the 15th day after initiating administration. No differences were observed between Japanese and European female volunteers in the pharmacokinetics of 3-keto-desogestrel and EE. During the period of multiple dose treatment, neither irregular bleedings nor side effects leading to dropouts were observed. (author's)     

高效液相色谱法对大鼠应用米非司酮的药物动力学研究

用高效液相色谱法测定大鼠ig（灌胃）和阴道给药米非司酮（均为16mg／kg）后0.5、1、2、4、8、24、48h的血清浓度，根据各鼠血药浓度-时间数据拟会曲线，ig呈二室动力学模型，阴道给药呈一空动力学模型，其Tmax分别为2.43h、4.50h；Cmax分别为320．60μg／ml、129．64μg／ml；Ka分别为0．84／h、0．67／h；T1／2分别为（1）0．88h、0．98h；（2）1．65h、15．07h；Auc分别为5153．1μg·h／ml，3155．99μg·h／ml；K10分别为0．12／h，1．06／h。结果显示米非司酮ig血药浓度较阴道给药血药浓度为高。     

Transfer of drospirenone to breast milk after a single oral administration of 3 mg drospirenone + 30 μg ethinylestradiol to healthy lactating women

Drospirenone (DRSP) is a synthetic progestogen which has been developed in combination with ethinylestradiol (EE) for use as an oral contraceptive (Yasmin^®, Schering AG, Berlin, Germany). The pharmacokinetic characteristics of DRSP were evaluated in serum and breast milk from lactating women who received a single oral dose of 3 mg DRSP + 30 μg EE, to determine the fraction of the dose of DRSP which transfers to breast milk. Nine healthy, lactating women were included into the present study and pharmacokinetic data were obtained from six participants. The maximum DRSP concentrations (data given as mean ± standard deviation) were reached on average 2.5 ± 1.2 and 2.8 ± 1.3 h in serum and breast milk, respectively after oral administration of 3 mg DRSP + 30 μg EE, and amounted on average to 30.8 ± 14.4 and 13.5 ± 11.7 ng DRSP/ml in serum and breast milk. The mean breast milk versus serum concentration ratios of DRSP increased from 0.16 to 0.57 within 2 h after dosing and decreased to 0.16 after 24 h. The average ratio of AUC_{0-48 h} values in breast milk versus serum was 0.23 ± 0.09. The mean DRSP concentration in breast milk over the 24-h period after dosing was 3.7 ± 1.9 ng/ml. The amount of DRSP measured to be transferred into breast milk in the six women participating in the present study was, on average, 635 ng (range 256.2–1357.9 ng) within 24 h, corresponding to about 0.02% of the maternal dose. Based on the average concentration of the drug in breast milk over 24 h and assuming a daily ingestion of approximately 800 ml breast milk, the daily dose that reaches an infant via breast milk is estimated to be approximately 3 μg DRSP. The subjective and objective tolerances of 3 mg DRSP + 30 μg EE were good, with no adverse events reported.     

Bioavailability of nafarelin in healthy volunteers.

The bioavailability of a single dose of intranasal nafarelin was evaluated in 15 healthy female volunteers. Each subject received a 400 micrograms intranasal and a 25 micrograms intravenous dose of nafarelin separated by at least 7 days. Blood samples were obtained frequently after each dose for determination of nafarelin plasma levels. After intravenous administration, time to maximum concentration (Tmax) was 2 minutes, and maximum serum concentration (Cmax) was 8.2 +/- 2.09 (SD) ng/ml. For intranasal nafarelin, mean Tmax was 18.4 +/- 7.9 minutes (range, 5 to 40 minutes), and Cmax was 2.04 +/- 1.29 ng/ml (range, 0.49 to 5.7 ng/ml). Systemic bioavailability of nafarelin ranged from 1.15% to 5.62% and averaged 2.82% +/- 1.23%. Nafarelin's bioavailability is adequate to achieve the desired therapeutic effect because of its inherent high biologic potency and its pharmacokinetic properties. Nafarelin is readily absorbed by the nasal mucosa, and therapeutic blood levels are rapidly achieved and maintained for a prolonged period of time.     

Effect of food on pharmacokinetics of cefuroxime axetil in Chinese subjects.

The effect of food on the pharmacokinetics of cefuroxime axetil was studied. Twelve healthy male subjects were included in this study. They were given single oral 500 mg doses of cefuroxime axetil alone or with food based on a balanced two-way crossover design. Plasma cefuroxime concentrations were assayed by the high performance liquid chromatographic method. When the drug was given alone, the area under the curve (AUC) was 15.77 +/- 4.12 mg*h/L, Cmax was 4.20 +/- 1.05 mg/L, Tmax was 2.36 +/- 0.84 h, T1/2 was 1.56 +/- 0.26 h, and Clp/F was 34.13 +/- 10.39 L/h; 45.12 +/- 9.59% of the dose was recovered in the urine within 24 hours, and the renal clearance was 12.58 +/- 4.41 L/h. When the drug was given with food, the corresponding AUC was 23.46 +/- 4.57 mg*h/L, Cmax was 7.10 +/- 1.41 mg/L, Tmax was 2.04 +/- 1.32 h, T1/2 was 1.40 +/- 0.23 h, and Clp/F was 21.93 +/- 5.18 L/h; the 24-hour urinary recovery was 69.33 +/- 6.13% and the renal clearance was 12.58 +/- 2.99 L/h. The above pharmacokinetic parameters obtained from the two regimens were compared by two-way ANOVA corrected for the change-over effect. No significant difference was found for Tmax, T1/2 or renal clearance (p > 0.05). Higher AUC, Cmax, urinary recovery and lower Clp/F values were observed for the regimen with food (p < 0.05). The plasma drug concentrations resulting from the regimen with food were higher throughout the 12-hour sampling period when compared to the regimen without food.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women.

In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms, two variants of rings were used in 20 postmenopausal women with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 microg/day and progesterone 20 mg/day, while the other (PI-003; n = 12) delivered the same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone, estradiol and progesterone were measured at pretreatment, weekly for 4 weeks, and then monthly for 4 months. The incidence of hot flushes, frequency of night sweats, mood scores, vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/ml for 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first 4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring, the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidence of hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment, owing to ring expulsion. Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring, although bleeding and spotting were confined to the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginal ring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.