Norplant

Norplant capsules and Norplant 2 rods contain levonorgestrel (LNG) that is released slowly for up to 2000 days. After removal the progestogen vanished from the blood stream within 96 hours, and fertility is restored in contrast to the pill contraceptives. Norplant provides a cervix barrier against spermatozoa. About 1/2 of women taking it had anovulation or luteinization of unruptured follicles. In ovulating women the midluteal progesterone values were clearly reduced. There have been some reports concerning the increased aggregation of thrombocytes and the decline of high density lipoprotein (HDL) cholesterol levels in Norplant users. Thrombosis, cerebro- and cardiovascular accidents have not been reported. A longterm prospective study of Norplant 2 users showed an unacceptably high rate of pregnancies after the 4th year, thus the rods have to be replaced after 3 years instead of 5 years. 23% of Norplant 2 and 41% of Norplant users had to resort to removal because of side effects. 54% of Norplant and 48% of Norplant 2 users halted use after 3 years because of menstrual disorders, irregular bleeding, depression, and mood changes. LNG has high affinity to sex hormone binding globulin (SHGB), and it is not active in bound form. The free LNG index was lower in women with unwanted pregnancies than in other women. In 1989 the Population Council reported on 7 phase-3 investigations involving 2470 women. Only 398 completed the 5-year observation period: the cumulative pregnancy rate was 3.5, there were 3 pregnancies among those with body weight of 50-60 kg and 8.6 pregnancies among those weighing 70 kg or more. There were 101 unwanted pregnancies, and 1 child was born with intersexual genitals. Endometrium biopsy or curettage is advised in the event of irregular bleeding especially in women over 40, and about 25% of Norplant users have undergone these procedures.     

Implantable contraceptives for women: effectiveness, discontinuation rates, return of fertility, and outcome of pregnancies

Progestogen-only contraceptive implants are highly effective. In most studies, 5-year cumulative pregnancy rates are less than 1.5/100 women for Norplant and Norplant II. No study has yet reported any failures with Implanon. Weight over 70 kg and age at insertion under 25 years both increase the failure rate of Norplant and Norplant II; however, data are as yet lacking for Implanon. The effectiveness of other progestogen-only implants for which there are as yet few data are unlikely to be any different. Continuation rates are high compared with other hormonal methods and with the intrauterine device. In most cohorts at least 35% of women, and often many more, are still using Norplant by the end of 5 years. Rates vary according to a number of factors, including population studied, age, and parity. Menstrual disturbance is by far the most common reason for discontinuation, with headache, acne, weight gain, and desire for pregnancy accounting for other common reasons for implant removal. Fertility returns rapidly following implant removal, and pregnancy rates (76-100% 1 year after removal) are usually no different from those following discontinuation of any other contraceptive method. There is no increase in the risk of ectopic pregnancy, fetal malformation, or impaired infant health in pregnancies conceived either during implant use or after removal.     

IMAP statement on Norplant subdermal contraceptive implant system

The Norplant implant system consists of 6 silastic capsules which deliver levonorgestrel to protect against pregnancy over 5 years. Clinical trials were conducted in 46 countries. The 5-year cumulative pregnancy rate is 3.9%. Norplant's efficacy falls as weight increases. Its failure rate is lower than that of combined oral contraceptives and most IUDs. Counseling is linked to acceptability. Medical personnel should be trained in counseling potential Norplant acceptors. They must undergo formal training in insertion and removal of Norplant. The first year and fifth year continuation rates are 75-90% and 25-78%, respectively. Bleeding irregularities are the main reason for discontinuation and the most commonly reported side effects. Levonorgestrel changes the cervical mucus and suppresses ovulation and the endometrium. Toxicological and teratological data on levonorgestrel and silastic show that Norplant is safe. It appears that Norplant does not cause any major pathological changes in the endometrium, liver, kidney, and adrenal and thyroid glands. Levonorgestrel in Norplant is linked to a slight increase in serum glucose levels which are not of significant consequence. Its effects on lipids and lipoproteins are not clear. Fertility returns to Norplant users shortly after removal. The return to fertility pattern basically matches that of other methods. Contraindications of Norplant use are confirmed or suspected pregnancy, previous ectopic pregnancy, breast cancer, cancer of the genital tract, cerebrovascular or coronary artery disease, acute liver disease, and undiagnosed abnormal genital bleeding. Norplant should be inserted subdermally in the upper arm during the first 7 days after menstruation begins. The capsules must be removed after 5 years if pregnancy is to be avoided. Before family planning programs provide Norplant, managers should make sure the staff is adequately prepared. Health personnel, counselors, potential users, and the public need informational materials on Norplant.     

Efficacy and continuation rates of Norplant in Pakistan.

A total of 265 women who had the Norplant system inserted were followed for 5 years. The present study is based on 11,435 women-months of use, describing the continuation rates and efficacy of Norplant among these women. The 5-year cumulative continuation rate was 45.7 per 100 continuing users. The continuation rates were age-dependent. The women > or = 35 years of age consistently maintained higher continuation rates at all time intervals as compared with those of younger women. During 5 years of follow-up, five women became pregnant. Three pregnancies occurred in year 2, one in year 3, and one in year 5. The 5-year cumulative pregnancy rate was 2.5 per 100 continuing users. The weight of the user did not influence the pregnancy rate. The continuation rates, as well as the pregnancy rates, are comparable to those reported from other countries in the region.     

WHO 86925 Norplant上市后监测(中国部分)

本课题研究目的是对Norplant皮下埋植剂潜在副作用进行监测,以进一步证实其安全性。对使用Norplant和IUD或绝育术的妇女进行比较随访研究。每半年随访一次,详细记录所有健康情况,共随访5年。随访率达99.9％。结果:Norplant组及对照组IUD和绝育术的5年继续使用率分别为76.25、80.89、98.10/100使用者。Norplant的5年累计妊娠率为0.6/100使用者,远低于IUD的8.11/100使用者,宫外孕发生率为0.46/1000妇女年,低于IUD的1.24/1000妇女年,但宫外孕和妊娠之比在Norplant组为31.6:100,远高于IUD的6.7:100,如发生妊娠,要警惕宫外孕的可能。月经问题是Norplant的主要终止使用原因,但使用5年者,其血红蛋白均值上升,和接收时相比P<0.001,而IUD使用5年者,其血红蛋白均值下降,和接收时相比P<0.01。在观察5年中胆囊炎胆石症、纤维囊性乳腺病在Norplant使用者中的发病率高于对照组,P<0.05～0.001,但未发现重大健康问题。Norplant使用5年是安全的。     

Norplant contraceptive implants: a new contraceptive for women

This article summarizes current knowledge on the mechanism of action, side effects, and effectiveness of Norplant contraceptive implants. The most common side effect of the implant method is its disruption of the menstrual cycle, especially in the 1st few months of use. Long intervals without frank bleeding may occur and be misinterpreted as pregnancy in women who have not been counseled about this possibility. The average annual continuation rate was 84/100 in a study of 324 women from several countries who were followed for 5 years after Norplant implantation. The net cumulative pregnancy rate for the 5-year study period was 0.6/100. Reasons for method termination included menstrual problems, other medical problems (headache, depression, fatique), planning pregnancy, and other personal reasons (change in marital status, change in residence). To provide training for doctors, nurses, and counselors, the Population Council has established a network of 5 training institutions. Within the next few years, drug regulatory agencies are expected to approve use of Norplant implants in many countries. Although at present the method is available only in Finland and Sweden, Thailand and Indonesia are considering the method and clinical trials are underway in India, China, Brazil, and the US. A consulting committee of the World Health Organization has concluded that Norplant implants are a suitable contraceptive method for use in family planning programs.     

Hormonal implants: the next wave of contraceptives

It will soon be possible for a woman who does not want to become pregnant to have a Norplant system implanted under the skin of her arm; it provides a 5-year supply of continuous hormonal contraceptive protection. Failure rates have been consistently below 1 pregnancy/100 users/year, and the system has generally shown continuation rates at least as good as IUDs. As with other contraceptives using progestins alone, the implant tends to disrupt menstrual patterns; a large proportion of women who stop using the method do so because of abnormal bleeding. However, menstrual disturbances appear to subside toward the end of the 1st year of use. The system consists of 6 separate capsules about 1.3 inches long and .1 inches in diameter made of silastic packed with 36 mg of levonorgestrel. Every day about 30 mg. of this hormone are released. The capsules are inserted in a fan-shaped pattern after a .2 inch incision is made; the entire operation, including preparing the patient and administering a local anesthetic, requires 10-15 minutes. Removing the implants is somewhat more complicated as the layer of fibrous tissue that forms around them must 1st be cut open. This procudure may take up to 20 minutes. The return of fertility does not appear to be compromised by the use of the implant. The 6-capsule Norplant system may be replaced in a few years by a more advanced 2-rod version that is now undergoing clinical trials.     

A multicenter comparative study on the efficacy, safety, and acceptability of the contraceptive subdermal implants Norplant and Norplant-II

In order to assess efficacy, safety, and acceptability of the contraceptive subdermal implants Norplant^® and Norplant^®-II in Mexican women, a comparative phase III clinical trial was undertaken in eight clinics across the country. The study involved 1052 women who were followed-up trimonthly for three years. Cumulative pregnancy rates were 0.29% and 0.34% for Norplant and Norplant-II implants, respectively. Similar overall cumulative discontinuation rates were observed at three years: 50.38% for Norplant capsules, and 50.44% for Norplant-II rods. The main method-related reason for termination was endometrial bleeding irregularity which led to discontinuation rates of 11.94% and 11.62% for Norplant and Norplant-II contraceptive systems, respectively. In 15,279 woman-months of experience accumulated with Norplant implants and 14,092 with Norplant-II implants, there were few adverse events reported. No difference was found between the two groups in either difficulty for implants placement and removal or women's discomfort, even though the time required for insertion and removal of Norplant capsules was longer than for Norplant-II rods. It is concluded that during the first three years of use, both implants systems are equally effective, safe, and acceptable.     

Efficacy and side effects of Norplant use in Thai women above the age of 35 years.

A prospective study of Norplant implant use in women aged above 35 years was conducted in Bangkok, Thailand. The purposes of this study were to evaluate the efficacy, menstrual patterns, and side effects of Norplant use in these women. A total of 100 women were recruited in a 1-year clinical study. Their mean age was 39.7 years. Most acceptors had completed secondary school. No accidental pregnancy occurred throughout the 1 year of use in this study. The most common menstrual pattern in these acceptors was amenorrhea followed by irregular bleeding. The major side effect was irregular bleeding. There was no significant change in systolic and diastolic blood pressure during the 1 year follow-up period. Thus, Norplant implant use in older women is a safe and effective contraceptive method. This should become another choice for contraception in women aged above 35 years who have contraindications for oral contraceptive use.     

Norplant use among urban minority women in the United States

The aim of this study was to develop a profile of urban American women who chose Norplant(R), determine factors associated with retention and early termination of implants, and to determine reasons for early removal. A total of 197 adult black and Hispanic women who had Norplant inserted were followed prospectively for up to 5 years. Interval and cumulative termination rates were calculated. Data were stratified by race and analyzed to include lost-to-follow-up (LTFU) subjects. Multivariate survival analysis was used to determine variables independently associated with termination. Cumulative continuation rates were 68% after year 1 and 13% after year 4. Significant predictors of retention included black race and lower parity. Probability of early termination increased with higher parity and Hispanic race. For black subjects, recent use of hormonal contraception was a predictor of retention. Menstrual changes and weight concerns were common reasons for removal. The Norplant 1-year continuation rate is lower than previously reported, but is higher than reported for oral contraceptives and Depo-Provera(R). Future studies should stratify by age, race, and parity, and use standardized terminology to report intervals of use.     

Five-year experience with Norplant

At Klinik Raden Saleh, Department of Obstetrics and Gynaecology, University of Indonesia, from 1 May until 31 August, 1981, Norplant contraceptive implants were inserted into 437 Indonesian women. The continuation rates of Norplant at first, second, third, fourth and fifth year were, respectively, 96%, 92%, 88%, 82% and 78%. Bleeding problems were the most common cause for removal. The cumulative five-year net pregnancy rate for Norplant was 1.8 per 100 women. The Norplant contraceptive system is thus seen to combine the highest acceptability as measured by its continuation rate with the highest long-term effectiveness among the available temporary contraceptive methods.     

国产皮下埋植剂多中心研究

目的:评价两种国产皮下埋植剂的避孕效果、副反应和继续使用率。方法:分两期进行。第一期为国产Ⅰ型、Ⅱ型皮下埋植剂与Norplant进行前瞻性临床对比研究,各100例,共300例。第二期为国产皮下埋植剂扩大临床应用,接受合格对象Ⅰ型999例,Ⅱ型998例,共1997例。随访5年。结果:5年随访率为99.5％。第一期国产Ⅰ型、Ⅱ型皮下埋植剂和Norplant的5年累计妊娠率分别为0/百妇女、1.0/百妇女、0/百妇女,5年继续使用率分别为77％、80％、80％,差异均无统计学意义(P>0.05)。主要副反应为月经紊乱,月经卡分析显示3种埋植剂的出血模型相似。第二期国产Ⅰ型、Ⅱ型皮下埋植剂5年累计妊娠率分别为0.20/百妇女,2.10/百妇女,5年继续使用分别为84.47％、82.28％。使用埋植剂6个月Ⅰ型和Ⅱ型月经问题主诉发生率分别为50.88％、57.16％,差异有显著意义(P<0.01),但随着使用时间延长,月经紊乱主诉发生率逐渐下降,两组间无差异。结论:5年研究表明两种国产皮下埋植剂的避孕效果、副反应发生率和继续使用率与Norplant相似,也是一种高效,长效的避孕制剂。国产皮下埋植剂Ⅱ型使用至第5年避孕失败率明显增加,建议国产Ⅱ型皮下埋植剂使用期限在3～4年为好。     

A five-year clinical evaluation of NORPLANT contraceptive subdermal implants in Bangladeshi acceptors

A non-comparative study of the Norplant contraceptive subdermal implant system was conducted in Dhaka, Bangladesh. The study was designed to evaluate the contraceptive efficacy, safety and overall acceptability of Norplant implants. Six hundred women were enrolled in the clinical trial, which began in 1985 at three study sites. Follow-up visits were scheduled at 1, 3, and 6 months after Norplant implant insertion, and every six months thereafter until removal or at the end of five years. There were no post-insertion pregnancies during Norplant implant use in this study. After five years of Norplant implant use, there was no clinically significant change in body weight, systolic or diastolic blood pressure. Less than 3% of the women ever reported having any significant medical problems such as migraine, respiratory or cardiac problems during the study. The gross cumulative continuation rate was 41.2 per 100 women at the end of five years. The two most frequently reported reasons for discontinuation during the study were menstrual problems and desired pregnancy. Of the women who completed the five-year user satisfaction questionnaire, the majority of the women (86.3%) planned to continue using contraception after study completion. Of these women, approximately one-third said they planned to use another Norplant set. The findings presented suggest that the Norplant system is a highly effective, safe and acceptable method among Bangladeshi women.     

Prolonged effectiveness of Norplant(R) capsule implants: a 7-year study

Soft tubing Norplant(R) contraceptive implants were studied in 1210 women for 7 years to measure the duration of effectiveness and the magnitude of the pregnancy rates over that time. Mean age at enrollment was 27.4 years. Of the enrollees, 42% were US residents. One-sixth (16.1%) weighed >/=70 kg at the time of implant placement. At the end of 5 years, the cumulative pregnancy rate was 1.1/100; at the end of 7 years, it was 1.9/100. No pregnancies occurred to any of the 400 women who enrolled in the study at age >/=30 years and who weighed <100 kg. Among women aged 18-33 years, the 7-year Norplant pregnancy rates are comparable to the median pregnancy rates of tubal sterilization methods for women of the same age and duration of use. For women aged >/=34 years, without regard to weight at admission, the 7-year effectiveness of soft tubing Norplant equals or surpasses that of tubal sterilization. For continuing implant users, annual pregnancy rates <1.0/100 in years 6 and 7, together with low cumulative pregnancy rates, testify that Norplant capsule implants remain highly effective for 7 years.     

Post-marketing surveillance of Norplant contraceptive implants: I. Contraceptive efficacy and reproductive health

The subject of this study to examine the safety and contraceptive efficacy of Norplant, we undertook a 5-year study of follow-up of women initiating use of Norplant, intrauterine device (IUD) or sterilization in eight developing countries. Women attending family clinics were enrolled if they consented and were medically eligible to use Norplant, IUD, or female sterilization. Women who chose to initiate use of IUDs or surgical sterilization served as controls and were frequency matched in 5-year age-bands with women who chose to use Norplant. At admission women had a physical examination, and their medical histories, demographic, and socio-economic characteristics were recorded. Follow-up visits were scheduled in the first 6 weeks after admission and semi-annually thereafter for 5 years irrespective of change of contraceptive method. Incidence rate ratios of health events were estimated for initial and current contraceptive method use. This paper reports reproductive health events and contraceptive efficacy. Altogether, 7,977 women initiating use of Norplant, 6,625 of IUD, and 1,419 of surgical sterilization were admitted. Their mean ages at initiation were 28.5, 28.5, and 29.6 years, respectively. More than 99% were married or cohabiting, and parous. Five-year follow-up was completed by 94.6% of the women. By the end of 5 years, the mean duration of first segment use per initiator was 4.16 years for Norplant, 4.10 years for IUDs, and 4.96 years for sterilization accounting for 39,337 woman-years for Norplant, 31,915 for IUDs, and 7,071 for sterilization. The study accumulated 78,323 woman-years of observation. Pearl pregnancy rates for Norplant, copper IUDs and female sterilization were 0.27, 0.88, and 0.17 per 100 woman-years, respectively. Users of Norplant, copper IUDs, and sterilization had rates of ectopic pregnancy of 0.30, 0.68, and 0.13 per 1,000 woman-years, respectively. Major health events related to the reproductive system were rare. Rates of acute PID were significantly lower among Norplant users than IUD users (p = 0.004). The rate of ovarian enlargement was significantly higher in Norplant users than controls (p <0.001), but not rates of hospitalization for this condition. Vaginitis and vaginal discharge, and low abdominal pain were significantly less frequent in Norplant users than in the other groups. Bleeding disturbances were more frequent among Norplant users than controls but not anemia. The study confirms the high contraceptive efficacy of Norplant, copper IUDs, and female sterilization. The incidence rates of major reproductive health problems were low. There was no significant excess of serious reproductive morbidity among users of Norplant compared to users of IUDs and sterilization.     

Norplant: what health educators need to know

The US Food and Drug Administration approved the contraceptive implant Norplant in December 1990. Many US physicians and nurse practitioners have received training in inserting the implant, but few health educators know enough about Norplant and potential users to provide adequate education and counseling. The 6-capsule system steadily releases 50-80 mg levonorgestrel into the bloodstream for five years for a contraceptive effectiveness rate greater than 99%. Levonorgestrel keeps the pituitary gland from releasing two hormones needed for ovulation, thickens the cervical mucus, and suppresses endometrial development. Irregular bleeding is the most common side effect. Contraindications for Norplant include liver tumors, active liver disease, breast cancer, active thrombophlebitis, unexplained uterine bleeding, pregnancy, blood clots in the eyes or lungs, diabetes, hypertension, and cigarette smoking. Advantages are its 5-year effectiveness period, that it is easy and convenient to use, does not require compliance, and is reversible. Disadvantages are that it offers no protection against sexually transmitted diseases, especially HIV/AIDS; it requires a surgical procedure; and its cost ($500-$750/patient). Few studies present a profile of US women using Norplant. Potential users are adolescents, vulnerable women, low income women with children, and women who do not want to become pregnant for a long time but do not consider the pill or sterilization viable options. Extensive research indicates that Norplant is safe in the short and intermediate term. More research is needed to identify the demographic profile of a typical user, why she chooses Norplant, how well she understands it, or whether she was well informed about it; to learn about satisfaction with Norplant; and to find out who discontinues Norplant before the end of 5 years. This information would help health educators in their counseling and education strategies.     

A 5-year clinical evaluation of norplant® implants in senegal

The principal objective of this 5-year clinical study of Norplant® implants was to introduce these implants into the family planning program in Senegal and to determine their overall acceptability and safety in Senegalese acceptors. A total of 300 subjects were enrolled into the trial from August 1986 to July 1991. All the women were followed-up for 5 years or until the implants were removed. The pooled cumulative discontinuation rate was 40.8 ± 2.91 per 100 women resulting in a continuation rate of 59.2 ± 2.91 per 100 women. Thirteen subjects (4.3%) were lost during the follow-up. Seven pregnancies were reported throughout the 5 years leading to a cumulative pregnancy rate of 3.3 ± 1.25 per 100 women. Menstrual problems were the reason most often given for early removal during the first 2 years. After year 2, desire for another pregnancy was the main reason for implant removal. The results presented in this study show that the Norplant implant system is a safe, effective, and acceptable method that meets the needs of the Senegalese family planning program.     

Pregnancy after removal of Norplant implants contraceptive

Many concerns have been expressed regarding the introduction of a new contraceptive method into family planning programmes. One of the concerns is the return of fertility after discontinuing the method. To evaluate the subsequent fertility status of the Indonesian women after removal of Norplant, a prospective longitudinal study was undertaken in Klinik Radeb Saleh, Jakarta. Fifty-one women whose Norplant were removed because of their wish to become pregnant were followed-up for a period of two years or until pregnancy occurred, whichever was earlier. Two groups of women who had Lippes C IUD removed or discontinued the use of DMPA for planning pregnancy served as control and were followed-up for equal length of time. The cumulative conception rate for ex-Norplant users, ex-IUD users and ex-DMPA users at one year was 76.5, 74.7 and 70.2 per 100 women, respectively. There was no significant difference between the groups (p greater than 0.05). The present study, along with other studies, indicate that the prolonged use of Norplant do not impair the return of fertility.     

Norplant使用者子宫内膜血管内皮生长因子、碱性成纤维细胞生长因子及转移生长因子β_1的研究

为探讨Norplant使用者子宫不规则出血的相关因素,对使用Norplant月经规律和有不规则子宫出血者的子宫内膜与正常子宫内膜的形态、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)及转移生长因子β1(TGFβ1)进行比较观察。结果显示:Norplant使用者子宫内膜无典型的周期特点,子宫内膜VEGF比正常子宫内膜减少,尤其是不规则出血组减少更为明显,但bFGF及GFβ1无明显差异。提示Norplant使用者子宫异常出血与子宫内膜VEGF的减少有关。     

NorplantR contraceptive subdermal implants: Two-year experience in Singapore

Norplant contraceptive implants are Silastic containing levonorgestrel implants. This study describes our two-year experience with 100 acceptors of Norplant implants in Singapore. No pregnancies occurred during the first two years of use. Desire for planned pregnancy and disruption of menstrual rhythm were the two main reasons for twenty implant removals during the two years. The continuation rate at the end of two years was 79%. The post-removal conception rate in women desiring pregnancy was 90% at the end of one year. It thus appears that the Norplant contraceptive system offers a highly effective, acceptable, reversible and safe method of contraception.