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.     

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。     

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.     

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.     

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.     

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.     

Transition from Norplant to Jadelle in a clinic with extensive experience providing contraceptive implants

OBJECTIVE: The purpose of this study was to understand the transition process from providing Norplant, the six-capsule first contraceptive implant system, to providing Jadelle, the two-rod second-generation system, in a clinical setting with extensive experience providing Norplant implants. MATERIALS AND METHODS: Two hundred forty-nine women requesting contraceptive implants from the PROFAMILIA clinic (Santo Domingo, Dominican Republic) were provided with information regarding the differences and similarities between the two implant systems being studied, including the easier insertion and removal procedures and the possible shorter use life associated with Jadelle. A questionnaire evaluating their preference and the reason why they chose either system was provided. The health care providers' opinions about the two systems were also studied. RESULTS: Fifty-three percent of the women preferred Jadelle over Norplant. The main reason behind their preference for Jadelle was its reduced number of implants with easier insertion and removal and less visibility in the arm, whereas that for Norplant was greater familiarity. Providers overwhelmingly preferred Jadelle. A 1-h presentation was sufficient training for providers experienced with Norplant. None had any problem with the management of Jadelle. CONCLUSION: The inclusion of Jadelle in a clinic with extensive experience with Norplant was easy and uneventful, but both methods should be available during a transition period of several months while confidence in the new method is being acquired by the community.     

Association between contraceptive method accepted and perception of information received: a comparison of Norplant and IUD acceptors

In the present study Norplant(R) and IUD acceptors who attended the same counseling sessions have been compared on their perception of the information received at the family planning clinic. The study covered 100 acceptors of each method quota matched by parity and years of schooling. Data were obtained through home interviews. The two groups presented no significant differences when selected socio-demographic characteristics were analyzed. Norplant users recalled more information on this method than did IUD acceptors, and the content of what they remembered was different. This included concepts as important as risk of pregnancy, menstrual and health effects, and method of removal. The results suggest that the intrinsic qualities of the new method and the presence of a group of women motivated to use one with its general characteristics, are not sufficient conditions for its acceptance.     

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.     

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.     

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.     

Health and growth of infants breastfed by Norplant contraceptive implants users: a six-year follow-up study

The objective of the study was to evaluate safety to infants whose mothers used Norplant levonorgestrel implants during breastfeeding. A nonrandomized clinical trial design was used. Participants were 220 and 222 healthy breastfed infants of mothers initiating use of Norplant or T-Cu IUD, respectively, at 55 days to 60 days postpartum. Infants were followed from birth through age 6 years. Breastfeeding pattern, infant growth, and disease events were recorded monthly in the first year, three-monthly in the second, and annually thereafter. Most mothers continued use of Norplant (96.4%) and T-Cu (94.1%) during lactation, and 2140 months of infant exposure to levonorgestrel were accumulated. Breastfeeding pattern and infants growth, from admission through age 6 years, were similar in both groups. In the first year, breastfed infants in the Norplant group had higher incidence rates (p < 0.05) of mild episodes of respiratory infections (adjusted RR 1.17, CI 1.08-1.27), skin conditions (adjusted RR 1.46, CI 1.20-1.79), and eye infections (unadjusted RR 1.49, CI 1.03-2.18) than the control group. Later on, a higher proportion of infants in the T-Cu group showed neurological conditions. Although breastfeeding patterns and infant growth is not affected by Norplant use during lactation, the effect on infants' health of steroidal contraception should be further evaluated.     

Comparative study on contraceptive efficacy and clinical performance of the copper/low-density polyethylene nanocomposite IUD and the copper T220C IUD

BACKGROUND: The study was conducted to compare the antifertility effectiveness and side effects of the copper/low-density polyethylene nanocomposite IUD (experimental group) and the copper T220C IUD (control group). STUDY DESIGN: One hundred females were randomly divided into two groups (experimental group and control group, n = 50 in each group). Clinical observation and comparative study were performed on the two groups for 12 months. RESULTS: Follow-up rate was 100% at the 12th month. In the experimental group and control group, the cumulative continuation rates were both 92.0 per 100 women at the 12th month and there was no difference between them (p > .05). The pregnancy rate, removal rate and expulsion rate were low with the difference being not statistically significant (p>.05). The most common side effects were excessive menstrual bleeding, spotting and pain. The rates of side effects were lower in the experimental group than in control group, especially during the initial 3 months after insertion with the differences being statistically significant (p < .05). CONCLUSION: The new design of the copper/low-density polyethylene nanocomposite IUD showed low pregnancy rate, high contraceptive efficacy and satisfactory acceptability. The study suggested that the TCu220C IUD also had high contraceptive efficacy, but had relatively more side effects.     

Post-marketing surveillance of Norplant((R)) contraceptive implants: II. Non-reproductive health(1)

This controlled cohort study aimed to evaluate the safety and efficacy of Norplant contraceptive implants in developing countries. Women initiating Norplant implants were index subjects and women initiating intrauterine devices (IUDs) or surgical sterilization were controls. Consenting participants at 32 clinics in eight developing countries were admitted and followed-up every 6 months for 5 years. Major and less serious health events during follow-up were recorded. Incidence rate ratios of health events adjusted for clinic were estimated for initial and current method use. This paper reports non-reproductive health events. The study involved 7,977 women initiating use of Norplant, 6,625 of IUD, and 1,419 of sterilization. Five years follow-up was completed for 94.6% of the women. The study accumulated 78,323 woman-years of observation. The initial method chosen accounted for 84.4% or more of observed woman-years in users of Norplant, IUD, or sterilization. Twenty-two of the recorded 34 deaths were due to accidents, suicide or homicide. Few deaths or major health events were due to cancer or acute cardiovascular diseases and were not associated with the contraceptive method used. The incidence rates of major health events were low and with two exceptions, there was no significant excess risk of serious morbidity for Norplant users compared with controls; among Norplant initiators gallbladder disease occurred at an incidence rate of 1.5 per 1,000 woman-years and was weakly associated with use of Norplant (rate ratio 1.52 [95% C.I. 1.02, 2.27]). For current Norplant users compared to controls, the rate ratio of a combined variable of hypertension and borderline hypertension was significantly elevated (1.81, [1.12, 2.92]). The occurrence of less serious health events was also low and several of them were significantly more often reported among Norplant users. Headache-migraine, weight gain, mood disturbances, pruritus, eczema, and acne had incidence rates among Norplant users of 11.5, 4.5, 2.8, 1.5, 1.4, and 0.9 per 1,000 woman-years, respectively, and were significantly higher than in controls. Respiratory health problems, nonspecific symptoms, and several ill-defined conditions were also significantly more often reported for Norplant users, but some of the excess incidence may be attributable to reporting and detection bias. The study confirms the safety with respect to serious disease of Norplant, IUDs, and sterilization.     

Ovulation detection following removal of levonorgestrel subdermal contraceptive implants

The time to resumption of ovulation following the discontinuation of levonorgestrel subdermal implants (Norplant) was assessed in 10 women. A blood sample (2 ml) was taken at the time of Norplant removal and then twice weekly until the first evidence of ovulation (serum progesterone concentration greater than or equal to 5 ng/ml) was documented. Ovulation was resumed in 80% of the cases by 3 weeks and in all the cases by 7 weeks. Prompt return of ovulation following Norplant removal is an additional advantage of this mode of long-acting contraception.     

Norplant皮下埋植避孕150例临床研究

目的:探讨Norplant皮下埋植避孕的效果。方法:选择Norplant皮下埋植避孕妇女150例作为治疗组,以宫内节育环避孕妇女150例作为对照组,比较两组使用情况、避孕效果和月经紊乱情况。结果:5年后随访,治疗组因不适取出32例,取出率为21.33%,其余118例全部达到避孕效果,有效率100.00%;期间出现月经紊乱58例,发生率为49.15%;对照组因不适取出或自行脱出10例,取出率为6.67%,其余140例中达到避孕效果115例,有效率82.14%,出现月经紊乱33例,发生率为23.57%。两组避孕效果、月经紊乱和不适失败率比较均具有统计学差异(P<0.01)。结论:对生育期要求避孕妇女行皮下Norplant埋植避孕手术可达到有效的避孕效果,但月经紊乱发生率相对较高,宫内节育环避孕有效率较皮下Norplant埋植避孕手术低,但月经紊乱发生率亦较治疗组低。使用Norplant埋植避孕如何减少月经紊乱,仍是今后值得探讨的一个问题。     

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.     

Norplant contraceptive implants: rods versus capsules

Norplant contraceptive implants are silastic implants containing levonorgestrel. When placed subcutaneously in the medial aspect of the upper arm, they release low levels of levonorgestrel in a constant manner over an extended period of time. Comparative studies of two silastic rods versus six capsules containing levonorgestrel were studied in 250 subjects for 4,464 months of use. Only one pregnancy occurred during the study. Side effect patterns were similar in both groups; the major side effect being irregular uterine bleeding. The bleeding, however, was well tolerated by subjects in both groups and discontinuation rate was very low. The two-rod system offers the advantages of easier insertion technique and shorter insertion time as well as ease of removal as compared to the six-capsule system. Norplant contraceptive implants offer a highly effective means of contraception which is particularly suited for women who are concerned about failure and compliance with oral contraceptives. This type of contraception should become well accepted, not only in underdeveloped countries, but in developed countries as well.     

Comparison of the clinical performance, contraceptive efficacy and acceptability of levonorgestrel-releasing IUD and Norplant-2 implants in China

The levonorgestrel-releasing IUD (LNG-IUD, 20 μg/d) and the Norplant^R-2 implants were studied in a randomized comparative clinical trial with 200 women for one year. No pregnancy or expulsion occurred with the Norplant^R-2. In the LNG-IUD group, there was one pregnancy at the 12th month of use after an unnoticed expulsion. The net cumulative pregnancy and expulsion rates of LNG-IUD were 1.0 and 3.0. The removal rate due to menstrual disturbances in both LNG-IUD and Norplant^R-2 groups was 3.0. The use-related discontinuation rates were 9.0 and 3.0, and the continuation rates were 90.0 and 96.0, respectively. The differences were not statistically significant.

Menstrual disturbance was the main side effect. It was improved after long time use, especially in the LNG-IUD group. After one year, the percentages of women with amenorrhea were 18.9 for the LNG-IUD and 8.3 for the Norplant^R-2. The menstrual blood loss was statistically significantly reduced in the LNG-IUD group, and blood haemoglobin concentration increased in both groups. The LNG-IUD and Norplant^R-2 are highly effective, safe, long-acting, and well accepted by the Chinese women.     

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.