国产18甲基炔诺酮皮下埋植剂和Norplant的临床比较性研究—666例 …

本文旨在研究国产１８甲基炔诺酮皮下埋植剂避孕的有效性及其副反应，与Ｎｏｒｐｌａｎｔ作比较，６６６例对象经过４年观察，。国产组共姓４例妊娠，４年累积妊娠经为１．０７／１００妇女，年平均妊娠率为０．２７／１００妇女，４年累积的续用率为７６．６／１００妇女。与国外Ｎｏｒｐｌａｎｔ组比较，都无统计学差异。     

Norplant皮下埋植避孕法使用七年临床观察

目的 评价单纯孕激素避孕埋植剂Ｎｏｒｐｌａｎｔ在我国妇女和的效果及副反应。方法 １９８４年始在１２个中心及其分中心接受使用Ｎｏｒｐｌａｎｔ避孕的妇女共有１０７１８名,采用前瞻性方法进行５年观察;其中部分妇女继续使用至７年,对使用７年的临床效果观察。结果 在第５年时的年妊娠率为０．６３／１００妇女。共有７５５４名妇女使用满５年,３６２２名妇女使用满６年,２４３３名妇女使用满７年。第６、７年的年妊娠率     

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     

药铜环165、活性γ型和TCu220C宫内节育器的多中心比较性研究

目的：为防止放置宫内节育器（ＩＵＤ）引起的月经过多，扩大含消炎痛和铜的２种不锈钢ＩＵＤ即药铜环１６５和活性γ型ＩＵＤ（γ－ＩＵＤ）的临床试验，并观察５年的效果、副反应和月经血量情况。方法：由全国１２所医院随机放置药铜环１６５、γ－ＩＵＤ各１０００例，以ＴＣｕ２２０ＣＩＵＤ为对照；放置后定期随访达５年，以生命表法统计效果；对其中各２０名志愿者于放器前和放置后定期进行月经血量测定。结果：５年时每百妇女的妊娠率，药铜环１６５为３．２、γ－ＩＵＤ为２．７、ＴＣｕ２２０Ｃ为３．２；每百妇女的脱落率各为７．７、２．３和２．４；每百妇女的因症取出率各为５．０、３．８和６．４；每百妇女的续放率各为７９．８、８８．７和８４．９。第１年内平均出血天数以药铜环１６５最短；月经血量测定说明γ－ＩＵＤ放置后血量减少，而ＴＣｕ２２０Ｃ明显增加。结论：药铜环１６５效果好，平均出血天数少，放、取技术同金属单环，易为基层接受；γ－ＩＵＤ效果好、出血少。二者均可推广。     

放置含铜宫内节育器的五年临床观察

对２００例放置金属宫内节育器（ＩＵＤ）失败的妇女，随机放置含铜ＭｕｌｔｉｌｏａｄＣｕ２５０ＩＵＤ（ＭＬＣｕ２５０）和ＶＣｕ２００ＩＵＤ（ＶＣｕ２００）各１００例。临床观察５年，随访率９７．５％。结果表明：ＭＬＣｕ２５０和ＶＣｕ２Ｏ０的５年累积脱落率为１．０／每百妇女（下同）、８．１；妊娠率为１２．０、４．１；因出血和疼痛取出率为６．０、６．１；继续存放率为８０．０、８１．７。ＭＬＣｕ２５０脱落率明显低于ＶＣｕ２００，两者比较，差异有非常显著意义。提示：ＭＬＣｕ２５０和ＣＶｕ２００５年存放率高，避孕效果好，两种ＩＵＤ均适合于放置金属ＩＵＤ失败者。ＭＬＣｕ２５０至少可使用５年，如增加其铜表面积，有可能使妊娠率进一步降低。     

高危妊娠引产中催产素应用的有关问题

本文总结６０例高危妊娠和３０例正常妊娠分娩过程，探讨了催产素静滴引产的有关问题。临床结果表明：催产素静滴催产的初滴速度５￣１０ｍＵ／ｍｉｎ是适宜的，是递增的梯度为０．５Ｕ／１００ｍｌ，即以０．５Ｕ／１００ｍｌ－１．０Ｕ／１００ｍｌ－１．５Ｕ／１００ｍｌ－２．７Ｕ／１００ｍｌ，最高３．５Ｕ／１００ｍｌ；其递增速率为１０ｍＵ／ｍｉｎ，即以１０ｍＵ／ｍｉｎ－２０ｍＵ／ｍｉｎ－３０ｍＵ／ｍｉｎ，最高７０ｍ     

皮下埋植剂移位2例

皮下埋植剂移位２例周雪明，张燕琳，陈孝路，屠兴复我们自１９９２年６月开展皮下埋植长效避孕，在取皮埋剂时，遇到２例原放置的皮埋剂发生移位，现报道如下。例１，２４岁，孕３产１，因已有１子并曾脱环３次于１９９３年１月１４日进行皮埋术，放置Ｎｏｒｐｌａｎｔ６...     

正常妊娠妇女外周血可溶性白细胞介素－2受体及淋巴细胞亚群的变化

测定了８７例妊娠晚期及２９例正常非孕妇女外周血可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平，同时对其中３６例孕妇及１０９例正常非孕妇女（正常对照）进行外周血淋巴细胞亚群检测。结果：妊娠晚期妇女ｓＩＬ－２Ｒ水平及Ｔｓ细胞（ＣＤ＿８）明显高于正常对照，分别为：２１４６００±７０４００Ｕ／Ｌ比１６２１００±８４１Ｄ０Ｕ／Ｌ，　Ｐ＜０．０１及３７．６％±５．３％比３１．３％±７．０％，Ｐ＜０．０１。妊娠妇女Ｔｈ细胞／Ｔｓ细胞（ＣＤ＿４／ＣＤ＿８）比例明显低于正常对照（１．２±０．２比１．５±０．５，Ｐ＜０．０１）。但总Ｔ淋巴细胞（ＣＤ＿３），ＣＤ＿４，细胞与正常对照相比，差异无显著性，分别为：６４．１％±７．３％比６６．０％±９．９％，Ｐ＞０．０５及４４．１％±５．８％比４３．８％±９．Ｏ％，Ｐ＞０．０５。相关分析表明孕妇ｓＩＬ－２Ｒ水平与ＣＤ＿３、ＣＤ＿４、ＣＤ＿８细胞及ＣＤ＿４／ＣＤ＿８均无显著相关性（ｒ分别为０．２０３２，０．２０７７，０．１０３７及０．１２１４，Ｐ均＞０．０５）。提示：孕妇外周血Ｔ淋巴细胞亚群及血清ｓＩＬ－２Ｒ的变化对维持正常妊娠有重要作用，ｓＩＬ－２Ｒ可能是促进胎儿正常生长的重要介质之一。     

两种国产皮下埋植剂多中心临床研究(扩大应用)(第一年随访总结)

本研究在全国11个省100个分中心对国产Ⅰ型和Ⅱ型皮下埋植剂进行临床多中心比较研究，共接收合格对象19673例，目前已完成一年随访。一年随访率95．9％，继续使用率分别为95．49％（Ⅰ型）和95．80％（Ⅱ型）。埋植后6个月和12个月时副反应发生率分别为5845％和4732％。副反应的发生率有随着时间的增长而减少的趋势。6个月时Ⅰ型皮下埋植剂和Ⅱ型皮下埋植剂副反应发生率较接近。12个月时到反应发生率1型皮下埋植剂（48．90％）显著地高于巨型皮下埋植剂（45．78％）（P＜0．001）。主要副反应为月经失调，约为副反应发生率的92％～94％。其中月经频发、不规则出血和点滴出血等问题发生率高于月经稀发和闭经。闭经、月经稀发／口量少和点滴出血的发生率Ⅰ型高于Ⅱ型。一年观察中，因月经问题而终止使用者占总终止人数的76％，与月经问题有关的一年累积终止率Ⅰ型为每百妇女3．44，Ⅱ型为3．21。一年的累积妊娠率Ⅰ型和Ⅱ型分别为每百妇女0．029和0．073，其间未见显著性差异。一年观察研究表明，两种国产皮下埋植剂的副反应发生率和避孕效果以及一年的续用率与进口的Norplant相似。     

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?     

A 10-year follow-up study of contraceptive Norplant implants.

OBJECTIVES: To evaluate the long-term efficacy and health problems associated with Norplant implants and re-implants after 5 full years of first implants. METHOD: From 1984 to 1988, 1657 women accepted first implants of Type I and Type II of Norplant, and 394 first acceptors had a re-implant, at a clinic for study. The clinical records and annual follow-up data of acceptors were analyzed. The life-table technique was the main method used. RESULTS: The continuation rates were very high. The cumulative pregnancy rates at 1, 3 and 5 full years of use were 0.0%, 0.1% and 0.7%, respectively. Users with heavier body weight had higher pregnancy rates. The rate of menstrual disturbances peaked at 73% after 3 months and consistently decreased to 20% at 5 years of use. Rates of menstrual disturbances associated with re-implants were much lower. CONCLUSION: Norplant is extremely effective and safe for long-term use.     

The significance of bleeding patterns in Norplant implant users

The purpose of this study was to examine the bleeding patterns of 234 Norplant users during 5 years of use and to identify the bleeding patterns of users who conceived. During the first year of use, 26.6% of users had regular bleeding cycles, 66.3% had irregular cycles, and 7.1% were amenorrheic. By the fifth year of use, 62.5% of users had regular cycles, 37.5% had irregular cycles, and none had amenorrhea. Of the ten users who became pregnant, eight had regular menstrual cycles in the 6 months before the diagnosis of pregnancy, one had an irregular pattern, and one did not keep a bleeding record. None had amenorrhea. The 5-years cumulative pregnancy rate for patients with regular cycles was 17.4%; this was significantly higher (P less than .05) than the 5-year cumulative rates of 4.4% in users with irregular cycles and 0% in users with amenorrhea. This study indicates that during the first year of Norplant use, only 26.6% of users have regular cycles, but after the first year, 50-60% of users develop regular cycles. The bleeding patterns of women using Norplant improve after the first year of use, and those with regular cycles are at greatest risk for method failure.     

Norplant implants: the mechanism of contraceptive action

OBJECTIVE: To determine if fertilization occurs unnoticed among Norplant users who are ovulatory. DESIGN: Serial blood samples were obtained during 1 month from sexually active Norplant users experiencing regular menstrual bleeding patterns and a control group of noncontracepting women trying to conceive. The sequential blood samples were assayed for the presence of human chorionic gonadotropin (hCG). SETTING: All samples were obtained from women receiving contraceptive service and health care at the Center for Research and Services in Human Reproduction and Contraception, Santo Domingo, The Dominican Republic. Assays for hCG were performed at the Department of Biomedical Sciences, University of Tampere, Finland. PATIENTS, PARTICIPANTS: A total of 32 women using Norplant implants were enrolled in the treatment group, and 20 women of proven fertility who were attempting to conceive served as a control group. INTERVENTIONS: Duration of Norplant use was as follows: 4 in the 2nd year of use, 13 in the 3rd year, 11 in the 4th year, 3 in the 5th year, and 1 in the 7th year. MAIN OUTCOME MEASURE: The determination of pregnancy was based on the presence of hCG in the luteal phase, using a sensitive and specific immunoenzymatic assay that can detect dimeric hCG as early as 7 days after ovulation. RESULTS: Nine pregnancies were detected. All were in the control group trying to conceive. Six of these advanced to clinical pregnancies, and three did not proceed beyond the next expected menses. None of the Norplant users had evidence of hCG production, whether the observed cycles were anovulatory or ovulatory. The probability of finding no pregnancies in the ovulatory months at risk among Norplant users is between 1 in 50 and 1 in 150,000. The null hypothesis that Norplant users conceive at a natural rate can be rejected at the 0.05 level. CONCLUSION: Interruption of early pregnancy (menstrual abortion) does not play a role in the mechanism of action of Norplant contraceptive implants.     

Norplant皮下埋植避孕法对子宫内膜影响的临床病理研究

<正> Norp1ant皮下埋植剂(以下简称埋植剂)避孕是一项新的、女用的长效避孕方法,避孕效果好,继续使用率高,可逆性强,已有44个国家355,000人应用。现将30例应用Norplant皮下埋植剂避孕妇女的31人次及埋植剂取出后置宫内节育器时采取子宫内膜3例介绍如下:     

Safety and efficacy of levonorgestrel implant, intrauterine device, and sterilization

OBJECTIVE: To evaluate safety and efficacy of levonorgestrel-releasing contraceptive implants (Norplant; Leiras Oy, Turku, Finland) in developing countries. METHODS: We used controlled cohort methodology. Women attending family planning clinics in eight developing countries selecting Norplant were enrolled, together with women of similar age choosing intrauterine devices (IUDs) or surgical sterilization. Participants were interviewed and examined at semi-annual visits and followed-up for 5 years regardless of change of contraceptive methods. Incidence rate ratios of health events were estimated for initial and current method use. RESULTS: Altogether, 7977 women initiated Norplant, 6625 IUD, and 1419 sterilization. The overall follow-up rate was 94.6% and 78,323 woman-years of observation were accumulated. Pregnancy rates for Norplant, copper IUDs, and sterilization each averaged less than 1 per 100 woman-years. With two exceptions, no significant excess risk of serious morbidity was detected for Norplant users compared with controls. The incidence of gallbladder disease was higher in women who initiated Norplant use than in controls (rate ratio 1.52, 95% confidence interval [CI] 1.02, 2.27), as was the incidence of hypertension and borderline hypertension in current implant users (rate ratio 1.81; CI 1.12, 2.92). Other new findings were increased risks of respiratory diseases and decreased risks of inflammatory disease of the genital tract in Norplant users compared with IUD users and sterilized women. CONCLUSION: The study confirms the safety with respect to serious disease and the high contraceptive efficacy of Norplant, copper IUDs, and sterilization.     

Long-acting hormonal contraception: assessing impact on bone density, weight, and mood.

The decline in unintended pregnancies and abortions in the United States has been attributed largely to increased use of two highly effective, hormonal contraceptive methods, depot medroxyprogesterone acetate injection (DMPA) and levonorgestrel implants (Norplant). Despite the efficacy and increasing acceptability of these long-term methods, some clinicians and women are reluctant to use them because of concerns regarding reduction in bone density with DMPA, and depressive symptoms and body weight issues with both injectables and implants. Recent multicenter experience showed no increase in depressive symptoms after 1 year's DMPA use and 2 years' Norplant use, even among users with the highest mean depressive symptom scores pre-therapy. Observational studies indicate that, as with other hormonal contraceptives and hormone replacement, DMPA does not cause significant weight gain, even during long-term use. Multicenter experience with the new soft-tubing Norplant product found an average annual pregnancy rate of <1% and a cumulative 5-year pregnancy rate of 4.2% in women weighing 70 kg or more--substantially lower than failure rates cited in the product labeling. Trends in bone density seen with DMPA appear similar to those during lactation. Subgroups of long-term DMPA users may experience a decrease in spinal bone density that appears to be reversible following discontinuation. A once-a-month injectable contraceptive combining 25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate (Cyclo-Provera, Cyclofem or Lunelle), a 2-rod levonorgestrel system, and a single-rod 3-ketodesogestrel implant system may become available in the United States. Large-scale trials have established the safety, efficacy, and acceptability of Cyclo-Provera. In contrast to DMPA, users of Cyclo-Provera experience predictable, regular monthly bleeding, fewer discontinue due to bleeding-related problems. Fertility returns rapidly following discontinuation. A U.S. multicenter study is currently nearing completion.     

NORPLANT皮下埋植避孕剂使用的有效性及其副反应的评价

本研究于1984年10月至1987年9月应用Norplant皮下埋植剂1470人(其中Nor-Plant-Ⅰ1169人,Norplant-Ⅱ301人)控制生育。12个月和24个月的避孕效果:累积的妊娠率分别为0.2%和0.3%,持续使用率分别为96.5%和86.2%。主要副反应:月经不规则是终止使用的主要原因;但总失血量不多。Norplant埋植剂使用1年和2年后测定血红蛋白均值略有升高;血压无变化;体重略有增加。埋植剂的放置和取出易于掌握,在1470名使用者中未发生感染或其他并发症,使用安全。由于其妊娠率低和不可能脱落及其高度可逆性,深为受试者所欢迎。     

Norplant

In this review of Norplant, the authors trace its historical development, explain its delivery system, and discuss clinical trials evaluating the method's efficacy and safety. Due to major problems associated with the use of long-term injectables, the Population Council began researching the use of subdermal capsules of Silastic that could serve as the basis for a long-term, reversible, steroidal contraceptive. After experimenting with several steroids, researchers settled on levonorgestrel, which by 1976 had become the most widely used progestogen in oral contraceptives. The traditional Norplant system consists of 6 Silastic capsules, each measuring 34 mm by 2.4 mm and containing 36 mg of levonorgestrel, which are inserted subdermally in the upper arm. The capsules are removed after 5 years (the article describes both the implantation and removal procedures). The Population Council has also developed a 2nd generation system known as Norplant-2. The authors discuss the pharmacokinetics and mode of action of the implant system, and survey the results of clinical trials performed in almost 30 countries. These studies indicate an overall cumulative 5-year pregnancy rate of 3.5/100. Fertility returns rapidly following removal of the capsules. None of the studies reports increased incidence of any particular problems in the pregnancies and infants conceived after Norplant use. Researchers have found a high degree of satisfaction with the system among Norplant users. There are, however, some side effects associated with Norplant use -- most notably, menstrual disturbances. Beneficial effects associated with Norplant use include protection against unwanted pregnancy and ectopic pregnancy. The authors conclude Norplant is an effective, safe, and reversible long-term contraceptive.     

Experience of Finnish women with Norplant insertions and removals

Objective Norplant® and Norplant-2® have been available for use by Finnish women since 1984 and 1986, respectively. The objective of this study was to explore Norplant users' experiences of insertions, removals and medical treatments.
Design A questionnaire was sent to women who had received Norplant® or Norplant-2® implants one to two years earlier ( n = 262) in normal clinical settings; the response rate was 79%.
Results At insertion, problems were experienced by 9% and at least some pain by 23% of women. During the first year 20% of all users (14% of Norplant® and 33% of Norplant-2® users) had their implants removed. Problems were experienced at removal by 33% of women and pain was experienced by 40%; nevertheless most users were satisfied with the device. Findings were similar for the two types of Norplant. Forty-two percent of the women had received minipills containing levonorgestrel before Norplant insertions in an attempt to assess Norplant's suitability, and 8% had received drugs for adverse effects caused by Norplant.
Conclusions Studies including perspectives of Norplant users and the whole lifespan of Norplant (including removal) should be conducted in all clinical settings where Norplant is provided.