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.     

A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant.

To compare the contraceptive efficacy, tolerability, and bleeding patterns, 200 healthy female volunteers received, in an open, comparative, randomized, multicenter study in China, either a single-rod (Implanon) or a six-capsule (Norplant) contraceptive implant for 2 years with an optional extension of up to 4 years. Women were exposed to Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. There were no pregnancies during the study. Per 90-day reference period, the median number of bleeding/spotting days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. Similarly, with Norplant, the median number of bleeding/spotting days decreased from 34.5 to 18.0-23.0 days, respectively. The number of bleeding/spotting episodes during year 1 was 2.0 per 90-day reference period with Implanon and 3.0 per period with Norplant (p < 0.05 for periods 1-4). For the remaining 90-day periods, there was no statistical difference between the two groups. In general, there was less frequent bleeding with Implanon compared with Norplant, whereas the incidences of amenorrhea and infrequent bleeding were higher with Implanon than with Norplant. The mean overall incidence of prolonged bleeding fell markedly during the study, from 66.0% in reference period 1 to 27.3% in period 16 with Implanon and from 69.0% to 21.7% with Norplant, respectively. The most common adverse events were related to disturbed bleeding patterns, which were also the major reasons for discontinuation (Implanon n = 8; Norplant n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Implanon was inserted in a mean time of 0.61 min and Norplant in 3.90 min (p < 0.001). Similarly, the mean time required to remove the implant was significantly shorter for Implanon than for Norplant (2.18 min vs 11.25 min, p < 0.001). The maximum time required for removal of the implant was 10 min for the Implanon group and 60 min for the Norplant group. In both groups, blood pressure and hemoglobin were not affected, whereas body weight tended to increase. It can be concluded that both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Compared with Norplant, there was less frequent bleeding with Implanon, whereas the incidence of infrequent bleeding and amenorrhea was higher. Implanon was significantly quicker to insert and to remove than was the multiple capsule system.     

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.     

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.     

Contraceptive implants and lactation

The safety and efficacy of four contraceptive implants, plant, Implanon, Nestorone and Elcometrine, have been evaluated during use in the postpartum period by lactating women. These implants provide highly effective contraceptive protection with no negative effect on breastfeeding or infant growth and development. Breastfeeding women initiating Norplant use in the second postpartum month experience significantly longer periods of amenorrhea than do untreated women or intrauterine device users. After weaning, the bleeding pattern is similar to that observed in non-nursing women. Norplant use does not affect bone turnover and density during lactation. Norplant and Implanon release orally active progestins while Nestorone and Elcometrine implants release an orally inactive progestin, which represents an advantage since the infant should be free of steroidal effects. The infant's daily intake of steroids (estimated from concentrations in maternal milk during the first month of use) range from 90 to 100 ng of levonorgestrel (Norplant), 75-120 ng of etonogestrel (Implanon), and 50 ng and 110 ng of Nestorone (Nestorone and Elcometrine implants, respectively). Nursing women needing contraception may use progestin-only implants when nonhormonal methods are not available or acceptable. Implants that deliver orally active steroids should only be used after 6 weeks postpartum to avoid transferring of steroids to the newborn.     

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.     

Nonpalpable ultrasonographically not detectable Implanon rods can be localized by magnetic resonance imaging

Recently, the contraceptive implant Implanon has been introduced in several European countries. In comparison to the six-capsule preparation Norplant, the removal of this single-rod system should be associated with less complications. However, the removal of nonpalpable Implanon rods can be difficult because the implant is not always visible with ultrasound. The aim of this study was to find a radiologic method for the localization of Implanon implants that are nonpalpable and can not be detected by ultrasound. X-ray, ultrasound, computed tomography, and magnetic resonance imaging (MRI) were investigated as methods to localize Implanon in a pig chest preparation and in a woman with a nonpalpable implant. The implant in the woman could be localized unequivocally only by MRI. We conclude that MRI is the best method for the unequivocal localization of nonpalpable, ultrasonographically not detectable Implanon rods. To avoid unnecessary scar tissue formation, it may be appropriate to defer surgery for the removal until definitive localization.     

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.     

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.     

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.     

Statement on Norplant subdermal contraceptive implant system

At its September 1985 meeting, the International Medical Advisory Panel of the International Planned Parenthood Federation drafted a statement concerning Norplant, the subdermal contraceptive implant system developed by the Population Council. The statement, intended for use by physicians, administrators, and other health personnel in the field of family planning, summarizes current knowledge of this means of fertility control. Norplant is particularly recommended for women who seek longterm protection from pregnancy, but either may desire another child in the future or do not wish to undergo sterilization. Insertion during the 1st 7 days after menstruation onset, or immediately postabortion or postpartum (in nonbreastfeeding women), is advised. Capsules should be removed after 5 years of use. Annual pregnancy rates range from 0.2-1.3/100 women/year, with a cumulative pregnncy rate of 5 years of 2.6. The most frequently reported side effect is irregular menstrual bleeding, especially during the 1st year of use. Continuation rates are 60-90% at the end of the 1st year, and about 50% after 5 years. Counseling, especially regarding bleeding irregularities, is critical to continued acceptability. 40% of women who request Norplant removal in order to conceive become pregnant within 3 months of removal, and 76% achieve pregnancy within 1 year. Epidemiologic studies of the longterm safety of Norplant implants are under way. It is noted that program use of Norplant poses several managerial challenges. Formal training in insertion and removal techniques, as well as the risks and benefits of the method, must be planned and back-up and referral facilities identified. Since Norplant is a new delivery system, a carefully designed public information system is also important.     

国产18甲基炔诺酮皮下埋植剂的临床研究

666例40岁以下健康育龄妇女所参加的前瞻性多中心研究,经过一年观察,国产组333例中无妊娠,对照的Norplant-1组发生1例妊娠,妊娠率0.3/100妇女,二组的续用率同为94/100妇女。     

Effect of Implanon use on selected parameters of thyroid and adrenal function

In this article, the effects of Implanon implant use on thyroid and adrenal function was compared with those of Norplant implants. In this 2-year open randomized study of 80 implant acceptors, we found that both implants may induce minimal changes in thyroid hormones and cortisol levels, possibly secondary to alterations in the respective binding globulins in the serum. These alterations in thyroid and adrenal function would have no clinical significance in healthy women. In the Norplant group, sex hormone-binding globulin levels decreased, whereas increased levels were found in the Implanon users at the end of 2 years. These findings lend support to the fact that etonogestrel, released from Implanon implants, is significantly less androgenic than levonorgestrel, released from the Norplant implants.     

Effect of etonogestrel subdermal contraceptive implant (Implanon) on liver function tests -- a randomized comparative study with Norplant implants

OBJECTIVE: The study aimed to assess the possible differences in effects of Implanon and Norplant implants on liver function over 2 years of use. METHODS: This is a 2-year open randomized study of 80 implant (Implanon and Norplant) acceptors. Selected parameters of liver function were tested in the serum before implant insertion and at 6, 12 and 24 months after implant insertion. RESULTS: In both the implant groups, the mean total and unconjugated bilirubin and the gamma-glutaryl transferase levels were significantly raised during implant use. For none of the subjects, at any sampling period, did the levels exceed the normal range in our population. There was no significant elevation of any other liver enzymes in either group. CONCLUSION: It appears that there may be mild hepatocellular dysfunction associated with the use of both Implanon and Norplant, which is possibly of no clinical significance to the healthy acceptor.     

Location and removal of non-palpable Implanon implants with the aid of ultrasound guidance

BACKGROUND: Implanon insertion appears to be an easy procedure, but in a small minority of cases difficulties have been encountered with removal if the rod is impalpable. METHODS: Patients were referred to the contraceptive and sexual health service with non-palpable Implanon. Following a clinical assessment and examination of the arm where the implant had been inserted, an ultrasound examination was carried out to identify and locate the implant. These implants were subsequently removed, some under general anaesthesia and others under local anaesthesia. RESULTS: Twenty-seven patients were referred to the unit with impalpable Implanon rods. In four cases the rods were palpable and were removed in the clinic setting without the need for further intervention. Positive identification of the implants was achieved in 21 of the remaining 23 cases using ultrasound. No implant was detected in two cases and etonogestrel was not demonstrated serologically in either woman, suggesting non-insertion. All 21 Implanon rods identified by ultrasound were successfully removed. In just over 52% of women a previous attempt at removal had been undertaken prior to referral. CONCLUSIONS: It is possible to identify and locate impalpable Implanon rods with the aid of ultrasound, facilitating their subsequent safe removal. Although previous reports have identified the position of 'lost' implants using ultrasound, this is the first case series to discuss measuring the skin/implant depth. This parameter, together with the precise position of the implant (in muscle or fat), aids removal. All health professionals inserting and removing contraceptive implants should have been appropriately trained.     

A comparison of the clinical performance, contraceptive efficacy, reversibility and acceptability of Norplant implants and Ortho Gynae T380 intrauterine copper contraceptive device

In this comparative study, the five-year continuity rate of 53.7% in the Norplant implants group was comparable to that of 52.7% in the copper IUD group. The difference was not statistically significant. Only one accidental pregnancy occurred during the five years of copper IUD use.Desire for future pregnancy was the main reason for removal in the Norplant implants group (35.9%) while expulsion of the IUD (13.2%) was the main reason for removal of the copper IUD. Menstrual disturbance was not a major side-effect in either group.The post-removal conception rates of 78.6% in the Norplant implants group and 75.0% in the copper IUD were good and comparable.Both the Norplant implants and copper IUD are acceptable and effective contraceptive methods in Singapore.     

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。     

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。     

皮下埋植避孕剂临床多中心对比研究

对两种国产皮下埋植避孕剂与 Norplant 进行前瞻性临床对比研究,以了解在避孕效果、临床副反应及续用率方面有无差异。全国10个省市分别承担国产Ⅰ型、Ⅱ型和 Norplant 各100例,采用前瞻性、随机化的临床对比研究。根据统一的科研计划、记录表格和定期随访,资料集中统计和处理。共接收国产Ⅰ型1 001例,国产Ⅱ型1001例,Norplant 998例。一年时的随访率为99.3%,1年内避孕失败1例,因各种原因的终止率分别为每百名妇女3.9、3.7和3.9,因月经问题而终止者分别占总终止的79%、73%和77%,一年末的续用率分别为96.1%、96.3%和96.1%,三组之间均无差异。两种国产皮下埋植剂均为一种高效的避孕方法,副反应发生率、因症终止率和续用率均与 Norplant 相似,在全国不同地区、不同群体之间和 Norplant 一样具有较高的可接受性,可供广大育龄妇女选用。     

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.