Norplant System contraceptive inserts

Note: This report represents the medical/scientific literature and AMA policy on this subject as of December 1997.

Full text

The NORPLANT SYSTEM (levonorgestrel implants, hereafter referred to as Norplant) is a long-term, reversible method that provides continuous contraception for as long as 5 years. Norplant was approved by the Food and Drug Administration (FDA) in December 1990 and received a 3B approval rating as a new delivery system offering a modest therapeutic advance over existing treatments. 

Norplant is comprised of 6 small, thin, flexible capsules made of soft Silastic (polydimethyl-siloxane) tubing measuring 34 mm in length and 2.4 mm in diameter, each containing 36 mg of levonorgestrel and sealed with Silastic medical grade adhesive (Silicone Type A). The capsules are inserted in a fan-like pattern in a superficial plane just under the skin of the upper arm in an office-based surgical procedure under local anesthesia and are removed in a similar fashion. The medical grade Silastic tubing is constructed of the same material contained in hydrocephalus shunts. The adhesive also has been used extensively in implants, notably cardiac pacemakers. Levonorgestrel, the active ingredient, is a potent progestin with some androgenic activity in animal-based studies.¹ 

Through 1996, at least 1 million women in the United States and more than 3.6 million women worldwide had been implanted with Norplant. However, its use in the United States has declined precipitously in the last 3 years because of widespread litigation and negative news media publicity. Some of the initial claims were based on pain or damage associated with insertion or removal of the implants. Plaintiffs also have alleged a wide variety of adverse events, many of which are common to hormonal contraceptives and are disclosed in the labeling. Plaintiffs have contended that they were not adequately warned, however, concerning the degree or severity of these events. Additionally, the silicone-based capsules of Norplant have served as an incentive for some plaintiffs and lawyers to claim injury on the heels of the silicone breast implant controversy. Currently, there are more than 2,700 Norplant suits pending in state and federal courts.²

In light of the controversy surrounding Norplant, the Council on Scientific Affairs (CSA) has examined the development of Norplant and evaluated its safety and efficacy, particularly as it applies to women in the United States. This informational report also briefly comments on the current role of Norplant and how circumstances surrounding its introduction may affect the future development of long-acting contraceptives in the United States.

AMA Policy

The AMA opposes requirements or incentives by government for the use of long-acting contraceptives³ (Policy H-75.991, AMA Policy Compendium). The AMA supports efforts by state societies to increase public aid coverage for implantable progestins and other methods of contraception and urges pharmaceutical manufacturers to reduce the price of implantable progestins for those segments of the population that are economically disadvantaged (Policy H-75.989). The AMA also supports congressional efforts to increase public funding of contraception and fertility research (Policy H-75.990).

Development of Norplant

The development of progestin-implant contraception began in 1966 at the Population Council's Center for Biomedical Research. The Council is an international nonprofit research organization based in New York City dedicated to improving reproductive health and helping to achieve a sustainable balance between population and resources. Initial clinical experience with a progestin released from Silastic capsules was reported in 1969.⁴ Over the next 5 to 6 years, various synthetic progestins were evaluated.⁵ By 1974, the 6-capsule drug delivery system was developed and the first clinical studies began in Chile. In 1975, a randomized, multinational phase III trial was initiated that compared subdermal implants containing either levonorgestrel or norgestrienone with the TCu 200 intrauterine device.^6,7 Other women were added to this cohort in 1978 to provide a larger data set for long-term follow-up.8,9 On the basis of its contraceptive efficacy, favorable toxicity profile, and worldwide use as an oral contraceptive, the Population Council in cooperation with its International Committee for Contraception Research selected levonorgestrel-containing implants for regulatory development. 

Phase III trials in the United States began in 1982. In 1983, the Population Council licensed Leiras Oy of Turku, Finland, to manufacture and distribute Norplant, and Finland became the first country to grant regulatory approval. Both the World Health Organization (WHO) and the International Planned Parenthood Federation later declared Norplant safe and effective for reversible fertility regulation.^10,11 The Population Council licensed Wyeth Laboratories to distribute the implant in the United States. By the end of 1992, 31 countries had granted approval and 55,000 women worldwide had experience with Norplant either in clinical trials or preintroduction studies. Norplant is currently approved for marketing in 58 countries.

Another type of levonorgestrel implant is comprised of 2 longer inserts (44 mm) each containing 75 mg of levonorgestrel crystals that have been homogeneously dispersed in polydimethylsiloxane, which is then polymerized into a solid rod and covered with a thin, steroid-free Silastic membrane. Previously referred to as Norplant-II, this implant was approved by the FDA on August 15, 1996, to provide effective contraception for up to 3 years. Marketing of the 2-rod system in the United States has been delayed while Wyeth-Ayerst conducts additional research on a new insertion device. In light of its experience with Norplant, the company continues to review the dynamics of the US contraceptive market to determine when a launch of the 2-rod levonorgestrel implant is feasible. 

Insertion 

Norplant should be inserted within 7 days from the onset of menses; however, the capsules can be inserted at any time during the menstrual cycle provided pregnancy has been excluded and an alternate nonhormonal form of contraception is used for at least the next 7 days.12 Under local anesthesia, a beveled trocar is used to insert the capsules subdermally in the midportion of the upper arm through a 2-mm incision about 8 to 10 cm above the elbow. Alternately, a sharpened trocar can be inserted directly through the skin.13 Distribution of the capsules should be fanlike, about 15° apart, for a total of 75°. The importance of proper insertion as a prelude to uncomplicated removal has been emphasized.14 Buffering lidocaine with sodium bicarbonate significantly reduces pain scores during infiltration anesthesia.15 

Wyeth-Ayerst and the Association of Reproductive Health Professionals (ARHP) cooperated to facilitate the launch of Norplant in 1991. Wyeth-Ayerst sponsored an ARHP traveling educational program on Norplant insertion for doctors, nurse practitioners, and physicians assistants in 37 locations around the country. Wyeth-Ayerst also coordinates and supports a nationwide educational program (Procedure Instruction Program) in which health care professionals who are experienced in insertion and removal techniques give hands-on instruction to other providers interested in learning these procedures. These programs have trained more than 28,000 providers on standard implantation and removal techniques; women were implanted free of charge.16 

Mechanism of Norplant's contraceptive effects 

As with progestin-only minipills, the contraceptive action of Norplant is believed to result from at least 2 primary effects: suppression of ovulation and thickening of the cervical mucus.

Norplant recipients exhibit variable ovarian activity. Ovulation is detected in less than 50% of cycles in Norplant users over a 5-year period when serum progesterone concentrations >3 ng/mL are used as an indirect measure of luteal activity.17-19 The proportion of users with luteal activity increases from less than 20% in the first 2 years, to 40% in the third and fourth years, eventually reaching 60% in the fifth year. Even when progesterone concentrations exceed 3 ng/mL in Norplant recipients, mean values are smaller than those of control subjects not receiving hormonal contraceptives, suggesting that corpus luteum function is still inadequate.19,20 Thus, inhibition of ovulation accounts for Norplant s contraceptive effect in at least 50% of the cycles, but regardless of their regularity the proportion of cycles marked by ovulation increases with time.

Because Norplant does not completely suppress gonadotrophin release, follicle-stimulating hormone and luteinizing hormone (LH) are released in adequate amounts to cause follicular development in many women.21,22 One half to two thirds of Norplant users with regular menstrual bleeding patterns after the first or second year of treatment appear to ovulate, but those subjects with evidence of follicular rupture have lower preovulatory LH surges and midluteal progesterone concentrations than untreated subjects.23-26 Because the LH surge may be inadequate to spur normal ovulation, persistent follicular enlargement can occur.24 In those who ovulate, contraception probably depends on cervical mucus secretions that are scanty, thick, and impermeable to sperm and luteal phase deficiency.20-23,27,28 Although the continuous presence of low concentrations of levonorgestrel can alter the normal growth and development of the endometrium, and theoretically its suitability for implantation of a fertilized ovum, subclinical abortion does not appear to contribute to the contraceptive effect of Norplant.29,30 

Pharmacokinetics 

Because the dosage of levonorgestrel cannot be titrated in Norplant users, the plasma concentration of levonorgestrel during the period of implantation is determined by the following patient variables: (1) body weight; (2) plasma concentrations of sex hormone binding globulin (SHBG); (3) systemic clearance of levonorgestrel; and (4) local factors that may limit diffusion, such as fibrous encapsulation of the implanted capsules and body fat. 

After insertion, the initial release rate of levonorgestrel is approximately 85 mg/day. This amount decreases to about 50 mg/day at 9 months, gradually declining to 35 mg daily at 18 months, and finally stabilizing at approximately 30 mg daily for the remainder of the 5-year period.31-34 The latter values are comparable to the oral dose delivered in levonorgestrel-containing minipills (30 mg, available in Europe) and the amount of levonorgestrel delivered from the racemic mixture of norgestrel (75 mg) contained in Ovrette.35 

Maximum plasma concentrations of 1.6 ñ 1.1 ng/mL are achieved within 24 hours of insertion. 12 At 3 months post-insertion, mean plasma concentrations of levonorgestrel are about 0.4 ng/mL. At 12 months, plasma concentrations (normalized to a body weight of 60 kg) are 0.33 ñ 0.12 ng/mL, and they continue to decline slowly in a linear fashion over the next 48 months to a mean value of 0.26 ñ 0.1 ng/mL.12,36 Levonorgestrel plasma concentrations correlate inversely with body weight; for each kilogram increment in body weight, the average plasma concentration of levonorgestrel decreases 0.0033 ng/mL. 12 These values are similar to those that are established 12 hours after an oral dose of 30 mg (0.2 to 0.3 ng/mL).37

Levonorgestrel binds with high affinity but low capacity to SHBG and with low affinity but high capacity to albumin. More than 80% of the steroid released from Norplant circulates bound to SHBG.38 Increases in SHBG (for example, caused by estrogen treatment) decrease the systemic clearance of levonorgestrel and lead to larger total plasma concentrations. Levonorgestrel itself depresses plasma concentrations of SHBG, and a significant correlation exists between the concentration of SHBG and the total plasma concentration of levonorgestrel.39 Changes in SHBG concentrations and the free fraction of levonorgestrel may account for individual differences in the degree of ovarian suppression occurring in the first 2 years compared with the last 3 years in women who retain the implant.40

There are marked individual differences in the metabolic clearance of levonorgestrel even after intravenous administration.41,42 Levonorgestrel is eliminated mainly by hepatic reduction followed by glucuronide and sulfate conjugation.43 Metabolism is enhanced by phenytoin and carbamazepine, and probably other drugs that induce cytochrome P450 as well.12,44 After single oral doses of levonorgestrel 30 æg to 150 æ g the mean elimination half-life was 13.7 to 19.3 hours.37,41,45,46 After multiple oral doses of levonorgestrel 150 mg the mean elimination half-life was in the same range (17.4 hours).47 Values were considerably higher (42 ± 16 hours) after implant removal.48 Nevertheless, according to the manufacturer, serum levonorgestrel concentrations fall below 0.1 ng/mL within 96 hours after removal of Norplant and are below the detection limit of 0.05 ng/mL within 5 to 14 days.12 The pharmacokinetics of levonorgestrel have been reviewed.49

Contraceptive efficacy 

Norplant is highly effective; the average annual gross pregnancy rate over 5 years is <1%.34,50,51 Return to previous fertility is usually prompt after Norplant is removed.52,53 The contraceptive efficacy of Norplant is not dependent on user compliance and therefore, in contrast to other methods, its use effectiveness is the same as its theoretical effectiveness. Pregnancy may be more likely to occur among women with regular menstrual periods than among those who experience an altered bleeding pattern.54,55 Comprehensive analysis of the published data on Norplant's efficacy and safety is complicated somewhat by the fact that 2 different types of Silastic tubing were used in the years preceding submission to regulatory agencies. In studies for which recruitment was completed by 1986, subjects received an implant that contained more inert silica filler yielding a firmer tubing of higher specific gravity (or density) than the currently marketed ("soft") implant.51 The bulk of international efficacy data for Norplant and the ongoing long-term safety analysis involved women implanted with the "dense" capsules. Studies submitted to the FDA included only a subset of patients that received the "soft" capsules. These capsules release levonorgestrel at a slightly higher rate and their contraceptive efficacy appears to surpass that of the "dense" implant.34 There is currently no evidence that adverse reactions are different when comparing the 2 implant designs.

Summary of International Efficacy Data: International data on the efficacy of Norplant is summarized to provide a benchmark for comparison with the US experience. Three Norplant trials were initiated prior to 1980 by the International Committee for Contraception Research in a total of 6 countries involving 992 subjects. These trials used laboratory-made implants, and either straight or randomized assignment.53 The second phase of trials began in 1980 with large-scale production of the "dense" implant. Many of these were undertaken by government health or family planning agencies, International Planned Parenthood Federation affiliates, or university research groups, frequently in collaboration with the Population Council or Family Health International.53 The trials included thousands of women from Chile, China, Colombia, the Dominican Republic, Ecuador, Egypt, Finland, Indonesia, Sri Lanka, Thailand, Singapore, and Sweden. The pooled efficacy results of these trials are summarized in Table 1. More than 50% of the post-1980 data are accounted for by Chinese women who had a relatively low incidence of pregnancy. However, some pregnancies that occurred prior to Norplant insertion are included in this data, which tends to artificially elevate the pregnancy rate. Women from the United States accounted for approximately 7% of the total data set for the period from 1980 to 1988. When the risk of pregnancy was analyzed by body weight, the gross cumulative rate for women heavier than 69 kg rose to 6% by month 36 of implant use, and it differed significantly from the risk in women weighing between 50 and 69 kg (<2%), and in those under 50 kg (0.2%).53

Table 1. Annual pearl pregnancy rate per 100 (Women years) of use53 

Clinical trial period	Year of Use 1 2 3 4 5
Pre-1980	0.3 (894)	0.2 (568)	0.5 (422)	1.5 (326)	0 (281)
1980-88	0.2 (12,133)	0.2 (5,806)	0.9 (1,632)	0.5 (1,163)	1.1 (835)

The outcomes of pre-introductory international clinical trials of Norplant begun by Family Health International in 1984 and the Population Council in 1985 involving 16,282 women between the ages of 18 and 40 have been analyzed.50 All of these studies used the "dense" Norplant capsules. In 1988, these organizations created a combined data base. Gross cumulative pregnancy rates were <0.6/100 women in the first year and <1.5 in the second year for all countries. In countries where 5-year follow-up data were available, the median cumulative pregnancy rate was 0.8/100 women. Significant increases in the cumulative 5-year pregnancy rate occurred with increasing body weight, similar to the trend previously noted.53 

FDA approval data: Material submitted to the FDA in support of the New Drug Application (NDA) for levonorgestrel implants included 7 phase III trials with an enrollment of 2,470 women from 8 countries.34 Annual and cumulative pregnancy data from these trials are summarized in Table 2. Approximately 16% of these women (n=402) received the "soft" implant, 60 of whom were American women. A total of 396 American women, or 16% of clinical trial participants, were enrolled at 3 sites. Additional safety and efficacy data were included from several international preintroduction trials (see above) involving over 16,000 women who received the "dense" implant. Importantly, subgroup analysis indicated that the gross cumulative 5-year life table pregnancy rate was only 1.1 per 100 users of Norplant who received the "soft" capsules, and, furthermore, contraceptive efficacy in these women did not differ by body weight, perhaps reflecting the higher release rate of levonorgestrel from "soft" tubing.34

Table 2. Annual and five-year cumulative pregnancy rates per 100 users by weight class in phase III trials.12,34

Weight Class	Year 1	Year 2	Year 3	Year 4	Year 5	Cumulative
<50 kg 50-59 kg 60-69 kg ³70 kg All implants "Soft" implant	0.2 0.2 0.4 0 0.2 0.2	0 0.5 0.5 1.1 0.5 0	0 0.4 1.6 5.1 1.2 0.4	0 2.0 1.7 2.5 1.6 0.5	0 0.4 0.8 0 0.4 0	0.2 3.4 5.0 8.5 3.9 1.1

Thus, the accumulated data from a variety of settings indicate that the contraceptive efficacy of Norplant is comparable to that of tubal ligation.

Removal

The standard technique for Norplant removal uses a 4-mm incision close to the distal ends of capsules.12 Removal times generally are measured from the initial incision until removal of all 6 capsules is complete, and do not account for preparation and anesthesia time. Capsules are located one at a time by palpation, and the tip is moved toward the incision where it can be grasped from below with curved forceps. Traction on the hemostat moves the implant down to the incision where the fibrous tissue sheath is removed, the exposed tip is grasped, and the implant is extracted through the incision with a straight forceps. Alternately, the body of the capsule can be impaled and lifted out. Removal may be complicated by the fibrous tissue envelope, which impedes manipulation and movement of the implants. Obesity, improper (deep) insertion, and capsule migration or deformity also may impede palpation and create additional difficulties for removal. Furthermore, the silicone tips can be difficult to grasp, particularly if they are deep or misplaced away from the incision.An empirical clinical scoring system has been devised to predict difficult removals based on the implants visibility, apparent arrangement, and position (VAP score). If a difficult removal is anticipated based on this value, measures can be taken to ensure that an experienced provider is present at the time of removal, or appropriate referral can be made.56 

Several alternate approaches to Norplant removal have been described. The "pop-out" method is the least invasive but is suitable only for superficial and well-placed implants; removal times in experienced hands average 20 minutes.57 The hook-traction and needle localization techniques are intended primarily for difficult-to-remove implants.58,59 In a pilot study of the Emory method, 44 of 50 removals were accomplished in less than 10 minutes.60 This technique requires more anesthetic and subcutaneous tissue dissection and a much longer incision (1 cm) than other procedures, which may be cosmetically unacceptable to some women. 

The "U" technique employs a 4-mm vertical incision between capsules 3 and 4, parallel to the implants and near the distal ends. Implants are grasped perpendicular to the long axis with a modified vasectomy clamp, pulled toward the incision and partially raised by lifting the handle toward the patient's shoulder. The fibrous envelope is opened and each implant removed with a hemostat.61 In a pilot study involving 38 patients, the average removal time was 7 minutes compared with almost 20 minutes in patients subjected to the standard technique. Also, fewer capsules were damaged during extraction with the "U" technique. A modification of this technique has been reported.62 

Results of pilot studies describing these alternate approaches are limited in application because they have involved only the developers of the innovation. The "U" technique is the only method that has been compared with the standard technique in inexperienced physicians. In 2 randomized trials, inexperienced physicians required fewer repetitions with the "U" technique to achieve a consistent level of performance, and implant removal was accomplished in a shorter period of time with fewer complications as compared with the standard technique.63,64 In one study, mean removal times decreased from 16 minutes to 9.9 minutes with the standard technique, and from 11.4 minutes to 7.8 minutes with the "U" technique over 10 trials. Eleven percent of procedures in the standard group took longer than 20 minutes compared with none in the "U" technique group.63 In the other study, mean removal times were 7.9 minutes versus 10.8 minutes in physicians who employed the "U" and standard technique, respectively.64 The latter value is similar to that reported in a recent international multicenter comparison of the 2-rod levonorgestrel contraceptive implant with Norplant. In experienced hands, the mean removal time for Norplant was 10.4 ± 8 minutes.65

These results appear to contrast significantly with those reported from one large multicenter study, which included women implanted between April 1991 and April 1992 at both family planning clinics and private practice sites.66 Approximately 50% of removals took longer than 30 minutes, and slightly more than 19% took 60 minutes or more. About 5% of patients had to return for a second visit to complete the removal, and nearly 25% of patients described the pain associated with the procedure as significant. These results were based on a patient survey administered after the removal procedure was concluded. Because it was not specified whether the removal times were estimated from the start of patient preparation, the beginning of infiltration anesthesia, or from the initial incision, these results cannot be directly compared with those above.

According to the product labeling, the removal complication rate was 6.2% in clinical trials.12 A complicated removal was defined as prolonged probing or extended removal time (limit not specified), multiple incisions, failure to completely recover all implants, pain during removal, and fainting (Christine Horzepa, Population Council. Personal communication, July 23, 1997). Complications were reported in 4.5% of removals, most often related to broken or misplaced capsules in preintroductory trials involving more than 3,400 women from 11 countries.67 These rates are one third to one half those reported during the training of inexperienced physicians in which complicated removals were defined as those that exceeded 20 minutes, and (applying the same definition) much lower than the rate occurring in the multicenter study of Frank et al. 63,66 These results reflect the fact that attainment of proficiency in both insertion and removal of Norplant is characterized by a learning curve, and if the capsules are not implanted properly, removal is more difficult. Even with ideal placement, practitioners may require ³5 trials to become proficient in removal.64 Experienced clinicians require a much shorter time period to accomplish removal with fewer complications. For example, in the international longitudinal safety analysis, removal difficulties have occurred in only 1% of patients because they were treated by highly experienced practitioners (Olav Meirik MD, PhD, World Health Organization. Personal communication, July 18, 1997).

Removals that exceed 30 minutes may become self-defeating because of tissue swelling. These women require a second visit to complete the removal process after the incision has healed. 

Localization of nonpalpable capsules: Implanted capsules sometimes cannot be palpated and removed expeditiously without more extensive tissue dissection. When difficulty locating capsules is encountered, diagnostic ultrasound imaging using a 7 MHz linear transducer or plain film radiographs of the insertion site may be sufficient to locate the capsules. Alternatively, an anteroposterior radiograph of the upper arm can be obtained using a soft-tissue technique followed by sonography to locate the capsule and allow precise marking of the overlying skin.68-70 Lost capsules that are not visualized with either plain film radiography or ultrasound imaging of the insertion site have been located with compression film screen mammography.71 Alternatively, difficult removal has been expedited under fluoroscopic guidance.62

Patterns of Norplant use and discontinuation

Because Norplant is intended as a long-term method of contraception, information on the discontinuation rate is important. Due to the high upfront cost, the duration of implant use also affects the potential pharmacoeconomic benefit of Norplant. 

The majority of long-term (ie, 5-year) data on Norplant use and patient acceptance has been obtained from international sites, particularly China, the Dominican Republic, Finland, Egypt, Chile, Indonesia, Sri Lanka, Egypt, and Bangladesh.50 Continuation rates vary from country to country because a woman's acceptance of Norplant varies based on religious and cultural differences concerning contraception, her tolerance of side effects, and the directives or attitudes of service providers. A summary of continuation rates obtained from the Family Health International/Population Council combined data set appears in Table 3. The ranges in Table 3 are based on those countries where 5-year data were available. Subgroup analysis of the combined data set revealed that younger age and low parity predicted early removal. Desire for pregnancy, menstrual problems, and personal wishes were the major reasons for discontinuation.50

Table 3. Norplant yearly continuation rates reported in international trials50

Studies Involving Women From the United States:  Premarketing: There are few published data about the experiences of American women from phase III or preintroductory trials. One survey using a nondirective questionnaire involving women from San Francisco reported on 205 of 250 women enrolled in a 5-year trial of Norplant, 70% of whom actually received the 2-rod levonorgestrel system.73 All Norplant acceptors were analyzed together because "performance was similar." The implant was removed from 54% of the women who were surveyed within 5 years, representing a geometric average annual continuation rate of 85%. 

Women participating in this study were selected from a somewhat broader socioeconomic group than was typical of most other postmarketing studies. These women selected Norplant primarily because of problems with past contraception, perception that it was easy to use, and belief in its long duration of contraceptive effectiveness. Most Norplant users experienced at least one unpleasant side effect including menstrual changes (82%), weight changes (32%), headaches (24%), mood changes (16%), and acne (15%). Side effects were the main catalyst for discontinuation. Those who opted for early removal were more likely to experience weight gain and acne.

Postmarketing:  Phase III and preintroductory clinical trials did not include adolescents (<18 years of age) or nulligravid women. However, a considerable portion of the published clinical experience concerning Norplant use by women in the United States is derived from family planning clinics whose clients are mostly young women of poor socioeconomic status, many of whom were adolescents. Typically, these studies were nonrandomized and involved evaluation of side effects (based on structured clinic or telephone interview), determination of continuation rates, and surveys of user satisfaction. They included observational, as well as prospective case-controlled studies, in which Norplant acceptors were compared with users of oral contraceptives and/or Depo-Provera. Most studies involved relatively short intervals (3 to 12 months) of observation and suffered from significant loss to follow-up. Selected prospective studies involving adolescents appear in Table 4, and those involving a mixed patient population appear in Table 5.

Results of prospective observational studies of adolescents who received the implant between July 1991 and July 1993 suggested its use was feasible in this population; 86% of users were satisfied and the removal rate at 6 months was similar in adolescents and adults (8% vs 6%).74 Results of another observational study conducted at an inner city clinic found that removal rates were much higher at 6 months (20%), eventually reaching 38% at 24 months. Those who retained the implant were more likely to have a previous history of induced abortion, but more than 50% of users scheduled office visits because of adverse events.75

Table 4. Norplant studies in adolescent subjects

Study Site/Population	Method/data collection	na/enrolled	Insertion dates	Norplant Removal	Comment
Surveys of Norplant Use
Family planning clinic 12-18 yrs and >18 yrs74	Prospective observational survey Phone interview	21/26	7/91-3/92	6 mo: 8%	86% of users satisfied
Inner city clinic Black and Hispanic 13-19 yrs75	Prospective observational study Chart review	98/122	6/91-7/93	6 mo: 19% 12 mo: 29% 24 mo: 38%	History of induced-abortion predicted retention
Comparative Studies versus Oral Contraceptives, Depo-Provera or Other Contraceptive Methods
Family planning clinic postpartum <17 yrs76	Prospective observational study Clinic visits, phone or chart review	NP 42/48 OC 42/50	9/91-7/92	11 mo: 2% 28 mo: 28% 40 mo: 60%	Norplant associated with higher rates of continued use and lower rates of pregnancy than OC
Family Planning clinic 11-18 yrs77	Prospective observational study Clinic visits or phone	NP 94/129 OC 94	3/92-11/93	6 mo: 0%	43% of OC users discontinued at 6 mos; 93% of NP users satisfied.
Family planning clinic 11-18 yrs78	Prospective observational study Clinic visits or phone	NP 56 OC 56		12 mo: 9%	Little diminution of side effects during second 6 month interval
Inner city clinic 12-18 yrs79	Prospective observational Clinic visit and chart review	NP 54/61 OC 64/80 Other Methods 48/67	4/92-10/92	6 mo: 13%	Mean satisfaction scores similar between Norplant and OC users; 50% of OC users discontinued

an = number of patients evaluated
NP = Norplant; OC = oral contraceptives

Several case-controlled studies have been conducted of Norplant versus oral contraceptives in adolescents.76-81 Oral contraceptives were discontinued by 43% to 50% of users within the first 6 months. Norplant was discontinued by £13% of users within the first 12 months and was associated with fewer pregnancies. Norplant users have reported both similar and lower degrees of satisfaction than users of oral contraceptives.79-82 

Two large observational studies of Norplant acceptors involving a mix of adolescents and adults found that age did not affect continuation rates up to 50 months post-insertion.83,84 Similar to the earlier findings, implant users typically had experienced problems with other forms of contraception.83 Retrospective analyses of patients implanted at 4 different provider sites (adolescent, resident, midwife, and family practice clinics) revealed that nearly 15% of acceptors who were contacted had discontinued the implant over a 7- to 25-month period.85 Similar side effects were experienced by retainers and removers, and neither age nor clinic site were related to the request for implant removal. Less than 60% of patients returned for follow-up care, and more than 25% of those who elected to have the implant removed did so at an alternate site, suggesting that when a large percentage of patients are lost to follow-up, discontinuation rates may be significantly underestimated.

 Table 5. Norplant studies in mixed patient populations

Study Site/Population	Method/data collection	na/enrolled	Insertion	Norplant Removal	Comment
Family planning clinics (81%) and private practice (19%) 11% teens66	Prospective observational Clinic visit, mail and phone questionnaire	967/1253	4/91-4/92	12 mo: 12.9%	Half of removals were < 30 minutes; >19% took one hour or more
Family planning clinic 43% teens86	Prospective observational study Query at the time of removal	2,358	8/91-5/93	6 mo: 7.8%	Removals prompted by bleeding, headache, arm pain. weight gain, hair loss, mood changes
Tertiary care medical center clinic84	Prospective Clinic visit	1688/1800	2/91-4/94	12 mo: 1.2%b 24 mo: 3.5% 36 mo: 7.9% 48 mo: 8.9%	Age did not affect continuation rates up to 50 months
OB/Gyn Clinic 20% teens83	Structured self-report form at routine follow-up, chart review, and telephone contact	136 teens (T) 542 adults (A)	3/91-8/92	6 mo: T 8%; A 10%  18 mo: 11%	50% of insertions were postpartum or postabortion
Family planning clinics Low income women87	Longitudinal Clinic and telephone interview	786/910	4/94-10/94	6 mo: 7.6%	Number of menstrual side effects most common cause for early removal
OB-Gyn Clinic Low income at high pregnancy risk 88	Prospective observational Clinic visits, routine and prompted	1,076	6/91-9/92	16 mo: 2%	Menstrual changes and headaches most common reason for removal Patients required 2 to 3 visits before removal

an = number of patients evaluated
b=Values were slightly, but not significantly smaller for adolescents

Two provider sites achieved very high continuation rates. One was a family practice clinic in a tertiary care medical center. Potential Norplant acceptors, 40% of whom were adolescents, received extensive personal counseling and were assured of rapid access and prompt treatment of complications. Cumulative continuation rates over a 50-month period were 93.6% in adolescents and 91.1% in adults.84 In the second study, only 2% of more than 1,000 women of lower socioeconomic class at high risk of unintended pregnancy had the implant removed within 16 months.88 This study employed similar methods to optimize the continuation rate. However, the removal procedure was performed only after 2 or 3 post-insertion visits, establishing that the problem was "ongoing, unresponsive to conservative treatment, and of significant concern to the patient," which raises the question of whether patients encountered or perceived barriers to early removal. 

Two other studies are noteworthy. Retrospective analysis of 208 Norplant acceptors attending a New York City family planning clinic indicated that 32% of women implanted between March 1991 and July 1992 and followed for a period of 15 to 31 months had discontinued use of the implant within 2 years; the mean duration of use was nearly 20 months.89 This population was comprised predominantly of women aged 20 to 30 years of lower socioeconomic class. This study is of interest because the facility doubled as a Norplant training center, yet the discontinuation rate was fairly high. In a large prospective study of 1,253 Norplant acceptors who attended either family planning or private practice clinics, 13% had the implant removed within 12 months. Neither age, income, racial and ethnic origin nor pregnancy history predicted method acceptability.66

Reasons for discontinuation

Adverse events are the most common reason for early removal of Norplant from women in the United States, particularly changes in menstrual bleeding patterns.86-88,90-92 Headache, weight gain, acne, hair loss, and depression or mood changes also prompted early removal, and some patients experienced arm pain or numbness after insertion of the capsules. Among low-income women, nonmedical reasons for having Norplant removed within the first 6 months of use were partner's desire for child within the next 2 years, perceived pressure from health care providers to choose the implant, and dissatisfaction with prior contraceptive methods. 87 Although women who discontinue Norplant before 5 years have been characterized by some as opting for early removal, in fact, many women never intended to use the method for 5 years.92

Results of the 1995 National Survey of Family Growth provide some revealing statistics about recent patterns of Norplant use in the United States.93 At that time, Norplant was used by approximately 1% of women practicing contraception. According to the survey, predictors of Norplant selection were:

Age: users tend to be younger women in their early 20s 

Parity: zero or only one child

Medicaid: women who are covered by Medicaid are about 4 times as likely to use Norplant

Region: use is lowest in the Northeast

Effects of negative news media coverage on Norplant use

News media coverage concerning Norplant litigation is generally thought to account for the large decrease in Norplant adoption. Gross sales data reflect the precipitous decline: annual sales peaked at $141 million in 1992 and fell 28% the following year to $101 million. At its zenith, 800 Norplant insertions were being performed daily. This had decreased approximately 90% by the end of 1995.94

Two preliminary reports suggest that negative news media coverage influenced the discontinuation rates of ongoing studies. One study examining long-term use of Norplant found that 28% of postpartum adolescents implanted with Norplant between September 1991 and July 1992 had discontinued the implant by 28 months, but this number more than doubled over the next 12 months.76,81 The accelerated rate of removal appeared to coincide with the onset of litigation and negative news media attention. At least 60% of the participants in this study were subsequently involved in litigation.81 Moreover, in a longitudinal study of 786 low-income women attending a family planning clinic who received Norplant between June 1993 and October 1994, exposure to negative news media coverage was one of the significant predictors of having Norplant removed within the first 6 months of use.87 

Safety of Norplant

Adverse events associated with Norplant are those that are caused by the hormone and those that are related to insertion and removal of the implant. The former are similar to those experienced with other progestin-only methods including irregular menstrual bleeding, headache, nervousness/anxiety, nausea/vomiting, dizziness, dermatitis, change of appetite, leukorrhea, mastalgia, ectopic pregnancy, delayed follicular atresia/ovarian cysts, and scalp hair loss.12 All currently available progestin derivatives also are associated with relative degrees of androgenic effects such as weight gain, acne, and hirsutism.

International data: The long-term safety of Norplant is being evaluated in an ongoing international effort coordinated by the World Health Organization-Human Reproduction Program, the Population Council, and Family Health International. The objective is to study the major side effects that have not been identified or could not be adequately evaluated in smaller clinical trials. Approximately 8,000 Norplant recipients were age-matched within 5-year bands with women who had been sterilized or inserted with a copper-containing intrauterine device (IUD). Preliminary reports provide reassurance concerning Norplant's low potential for inducing stroke (0.03/1000 woman years), visual disturbances (0.09/1000 woman years), ectopic pregnancy (0.3/1000 woman years), and gallbladder disease (1.21/1000 woman years) (Olav Meirik, MD, PhD, World Health Organization. Personal communication, July 18, 1997). Headaches, including migraines, occur more frequently in Norplant users than in those with an IUD. 

FDA MedWatch data: From the marketing of Norplant in February 1991 through December 1993, the FDA received about 5,800 reports on Norplant submitted to the MedWatch Reporting Program.92 Serious events included:

 Table 6. Norplant adverse events

Adverse event	Number reported
Pseudotumor cerebri Hospitalization for insertion site infection  Hospitalization for removal difficulties  Stroke  Thrombotic thrombocytopenia purpura Thrombocytopenia	39 24 14 14 3 6

The reporting rates for these occurrences fell below or within the expected rates in women of childbearing age, but because of the underreporting of adverse events to the FDA the author had some concern that the rare occurrence of stroke, thrombocytopenia, and pseudotumor cerebri may be associated with Norplant use.95  The author's statistical assumptions have been questioned.96 

The product labeling was revised in August of 1994 to note that stroke and myocardial infarction (Warnings) and pseudotumor cerebri (Precautions) have occurred in Norplant users. Serious adverse reactions reported in less than 1% of Norplant recipients were pulmonary embolism, superficial and deep venous thrombosis, thrombotic thrombocytopenia purpura, idiopathic intracranial hypertension, and stroke. Their causal relationship to Norplant use is unknown. In August 1995 the FDA reaffirmed its view that Norplant is safe and effective when used as directed.97 In October 1995 product labeling information pertaining to the possible occurrence of pseudotumor cerebri was moved to the section on Warnings. 

In 1995 the FDA received as many adverse drug experience reports concerning Norplant (5,712) as it had in the nearly 3-year reporting period described above, ranking it behind Aleve as the drug most commonly cited.98 This reflects, in part, the negative news media coverage and litigation concerning the implant. The total number of adverse drug reports for Norplant includes all complaints received by Wyeth-Ayerst in the course of litigation, including those that acknowledged only that the "patient suffered injury" (Margaret Weber, MD, Wyeth-Ayerst. Personal communication, July 18, 1997).

Menstrual irregularities:  The most significant side effect, because of its frequency and disturbing nature, is the alteration of the rhythm or periodicity of menstrual bleeding. This is a feature common to all continuous low-dose progestin-only contraceptive methods. Disruption is variable, between and within women, and changes with the duration of implant use. Irregular and frequent bleeding and spotting are usually the most common patterns, although amenorrhea also occurs. Menstrual irregularities were reported by 70% to 89% of American women in various studies. 

Bleeding changes do not increase total blood loss, induce anemia, or reduce measures of iron stores.99-102 The pattern of menstrual bleeding tends to become more regular after the first year of use, but up to 35% to 45% of users continue to experience irregular, frequent, or prolonged bleeding into the fifth year of use.55,103,104 Short-term treatment with ethinyl estradiol alone or combined with oral levonorgestrel reduces the number of bleeding plus spotting days, and can be used to reduce the duration of extended bleeding periods.105,106

Ectopic pregnancies and delayed follicular atresia: The use of progestin-only pills has been linked to an increased incidence of ectopic pregnancies, perhaps because progesterone may reduce the activity of fallopian tube cilia and delay ovum transport.107 However, the likelihood of an ectopic pregnancy depends on both the pregnancy rate and the proportion of pregnancies that are ectopic. The estimated ectopic pregnancy incidence in women not practicing contraception is 2.6/1000 women years.108 According to the product labeling, the incidence in Norplant users was 1.3/1000.12 In another group of studies encompassing 21,560 woman years of observation, the rate of ectopic pregnancies in Norplant users was 0.28/1000 woman years.53 As noted above, interim data from the longitudinal study also suggest that the risk of ectopic pregnancy in Norplant users is very low, on the average of 0.3/1000 woman years.The amount of levonorgestrel released from Norplant incompletely suppresses gonadotropin stimulation of the ovary and delayed follicular atresia sometime occurs. Rarely, this has culminated in torsion and pain justifying surgical intervention.

Metabolic effects: Progestins have the capacity to affect lipid and carbohydrate metabolism. The effects of a progestin on lipid metabolism are dependent on its dose and androgenic potency. Progestins with greater androgenic activity decrease high density lipoprotein (HDL) and HDL2-cholesterol in association with increases in hepatic lipase activity and decreases in apolipoprotein A-I and A-II; they also tend to decrease triglycerides and lipoprotein A, and to increase low density lipoprotein (LDL)-cholesterol.109-111 Studies involving oral administration of low doses of levonorgestrel and other progestin-only contraceptives to women with relatively normal lipid profiles indicate only negligible effects on lipid metabolism.107

Studies in Norplant acceptors indicate no effect on lipid metabolism or small but significant decreases in total cholesterol and triglycerides with variable effects on HDL- and LDL-cholesterol.111-114 In 6 studies submitted in support of the Norplant NDA, total cholesterol decreased and changes in HDL-cholesterol were variable. 34 Ratios of HDL- to total-cholesterol were either unchanged or increased. Therefore, it appears that Norplant does not adversely affect the lipid profile.

Decreased insulin sensitivity and deterioration of oral glucose tolerance curves have been reported with oral contraceptive use, parti cularly with those containing levonorgestrel.115 In studies that employed oral glucose tolerance tests, Norplant users also showed modest increases in glucose concentrations. In one study, insulin concentrations also were elevated suggesting some degree of insulin resistance.114,116 Studies that used the insulin tolerance test or mathematical modeling concluded that Norplant did not affect the apparent sensitivity to insulin in normal nondiabetic women. Reduced tissue sensitivity to insulin was still apparent when the hyperglycemic, hyperinsulinemic technique was employed.117-119 However, these changes are not clinically significant, nor do they appear to be progressive in women who are not diabetic.33

In general, progestin-only oral contraceptives have been found to exert little effect on coagulation activity.120 Studies of the effects of Norplant on clotting factors have yielded differing results. Both increases and decreases in factor VII and antithrombin-III concentrations have been reported, with either no change or increases in Factor X, platelet count, and aggregability.121-124 Thromboembolic and thrombotic events including stroke, myocardial infarction, and pulmonary and deep venous thrombosis have been reported in Norplant users, but the causal relationship is unknown.12 

In clinical trials submitted in support of the Norplant NDA, the incidence of weight gain associated with Norplant during the first year averaged 3.7% (Margaret Weber, MD, Wyeth-Ayerst. Personal communication, July 18, 1997). This is similar to the value reported in one 18-month observational study that included 20% adolescents.84 In some studies, adolescent Norplant users who gained weight experienced moderate increments (mean 2.6 to 6.4 kg) over 6 to 12 months, with isolated cases of very large gains.78,125 Additionally, weight gain has been commonly cited as a reason for early removal. On the other hand, results of another study involving a mixed age patient population indicate that Norplant acceptors do not exhibit weight gain, and may even experience weight loss.126 Weight gain should not be considered an inevitable consequence of Norplant insertion.

Silicone-based immune reactions: Since the possibility of an association between silicone-gel breast implants and connective tissue or autoimmune disease was raised, a large number of epidemiological reports and analyses have failed to establish a causal role between breast implants and systemic disease.127 Although the Norplant capsules provoke a typical foreign body reaction, the silicone elastomer is not an immune adjuvant and there is no evidence that it is associated with systemic disease despite being implanted in over 4.5 million women worldwide. A similar conclusion has been reached on the silicone elastomer components of cerebrospinal fluid shunt systems.128

Vaginal HIV transmission: Public health concerns were raised in late 1996 with the publication of a report that indicated monthly subcutaneous progesterone implants facilitated the infectivity of cell-free simian immunodeficiency virus (SIV) administered intravaginally during the follicular phase in rhesus macaque monkeys.129 Epidemiological evidence in humans is conflicting, but does not broadly support the concept that progestin-only methods such as Depo-Provera facilitate human immunodeficiency virus infectivity.130 Progesterone-induced changes in the monkey's vaginal and cervical epithelium that occur during the luteal phase appear to reduce anatomic barriers to SIV infection. Preliminary data based on human biopsies obtained from Norplant users suggest that the low concentrations of levonorgestrel released from Norplant do not induce thinning of the vaginal mucosa.131

Legal issues

Currently, there are more than 2,700 Norplant suits pending in state and federal courts.2 Most federal lawsuits have been consolidated in the Eastern District of Texas. In January 1995 Wyeth-Ayerst announced plans to "offer health care providers defense and indemnification in connection with claims and lawsuits associated with the Norplant System" as long as the contraceptive was prescribed, inserted, or removed according to labeling.132 On August 5, 1996, class certification was denied and the court dismissed the plaintiff's master class action complaint on the basis that individual claims predominated over common issues. The precedence for this point of law was the Fifth Circuit United States Court of Appeals holding in Castano v. American Tobacco. This action reversed certification of a nationwide class alleging nicotine addiction from cigarettes. Under Castano, individual trials are necessary in order to allow the court to make an informed decision regarding whether common issues predominate and whether certification of a class is superior to other methods for handling the litigation. The plaintiffs may reargue their motion for class certification following completion of individual trials. 

On February 24, 1997, the court granted the defendants (Wyeth Laboratories, Inc, and American Home Products) motion for summary judgment in the first of 3 such Norplant bellwether trials and dismissed claims for strict product liability, negligence, breach of implied warranty of merchantability, misrepresentation, and consumer fraud based on the Texas Deceptive Trade Practices Act. The court in issuing its ruling applied the learned intermediary doctrine. This doctrine holds that when a manufacturer sells a drug that is properly prepared and accompanied by proper directions and warnings to the prescribing physician (ie, the learned intermediary), the drug is not viewed as defective or unreasonably dangerous and the manufacturer is not liable for resulting damages nor is it responsible for warning each patient directly.133 Several state courts including Illinois, Pennsylvania, Arizona, and New Jersey have granted summary judgment involving Norplant, and an Illinois court has decertified a class of plaintiffs alleging removal difficulties.2

Conclusions 

Norplant is the most effective reversible method of contraception available, comparable to surgical sterilization in contraceptive efficacy. As a technical variation of existing progestin-only methods, it offers a long duration of action and high efficacy. The latter is due in part to the fact that patient compliance is removed as a variable in determining use effectiveness. The other major advantage of Norplant is the lack of estrogen. 

The average wholesale price of Norplant in the United States is $365 for a kit containing the 6 capsules, trocar, scalpel, forceps, syringes, and needles, skin closures, gauze sponges, bandages, and surgical drapes. Implantation and removal costs bring the total to about $700. Because Norplant lacks special public sector pricing, the large upfront cost is a factor in access to the method for some women. 

Because it is unintended pregnancies that drive the cost-benefit calculation, acquisition costs do not predict the relative economic merits of various contraceptive options. All methods of contraception generally are cost effective compared with the lack of contraceptive practice; their rank order is driven largely by their relative failure rates. Based on direct medical costs modeled from the perspectives of both a private payer (Medstat's Market scan database) and a publicly funded program (Medi-Cal), Norplant ranks near the top of contraceptive methods in terms of its economic value when measured over a 3- to 5-year period.134 

The continuation rates of Norplant represent a significant improvement in compliance compared with other (reversible) contraceptive methods. As such, it offers a potentially great benefit to women who are unable or unwilling to comply with other methods of contraception, and who are at high risk of unintended pregnancy. However, as with other hormone-based methods, the use of Norplant is associated with adverse events including irregular bleeding, headache, weight gain, acne, and hair loss or hirsutism that lead many women to opt for early removal. In retrospect, this should perhaps not be surprising given the relative lack of popularity of progestin-only minipills. Although most of the adverse events associated with Norplant are predictable, not life-threatening, and often referred to as "not serious," they are at the very least annoying to many women and distressing to some. These adverse events affect quality of life, particularly among poor or young women who may not have ready access to health care. These types of adverse events tend to be minimized because they are not considered risks per se as would be for example stroke, idiopathic intracranial hypertension, or myocardial infarction¾although, as noted above, the causal relationship between Norplant use and these life-threatening events is not established. 

Other disadvantages of Norplant include the requirement for surgical procedures, its visibility, the lack of dosage titration, potential removal problems, and skin scar formation. Thus, the keys to a woman's acceptance and continued use of Norplant are individual counseling, proper insertion, ready access when complaints or adverse events arise, and the availability of facilities for timely and safe removal. 

The introduction of a long-acting contraceptive that once implanted could not be voluntarily reversed created a new set of problems. Proposed uses of Norplant as a judicial remedy or as an instrument of social engineering, and the fact that its pattern of use involved a majority of women of poor socioeconomic class, contributed to public mistrust. Such thinking led to indictment of Norplant in the United States before sufficient long-term experience could be obtained. Results of a study that empirically examined the issue of Norplant coercion found that the reality of coercion has been far less dramatic than the threat.135 No state laws have been enacted linking welfare payments to Norplant use, judicial rulings that made probation for abusive mothers conditional on Norplant use have been negatively sanctioned, and only rarely have women reported pressure from a counselor or health care provider to accept Norplant.

Concern also was raised that Norplant users who were otherwise healthy might neglect or defer health maintenance activities because they no longer had to maintain annual visits for contraceptive services, including prescription refills. Missed opportunities to screen for sexually transmissible diseases (STDs) and cervical dysplasia could obviate other advantages of this contraceptive method. Results of some observational studies involving low-income women and adolescents revealed that, indeed, Norplant users failed to appear for follow-up visits at a high rate, but there was no evidence in short-term studies that Norplant users were at higher risk of incidence of STDs or of reduced condom use, or that their behavior differed from women using other hormonal methods.136 Furthermore, these concerns also apply to users of condoms, IUDs, and those who have been sterilized and, therefore, should not be used to condemn the implant.

The controversy surrounding Norplant does not diminish the extent of its initial success, which proved that women in the United States have a keen interest in contraceptive methods that are highly effective, long-lasting, and readily reversible. Sales of Norplant skyrocketed in 1991 and 1992, dropped off somewhat in 1993, and then plummeted as widespread litigation unfolded. The initial demand for Norplant outstripped available services in some locations. This demand may have exacerbated an imbalance between the number of trained and experienced providers and the number of woman seeking the implant. Achievement of competence in both Norplant insertion and removal is characterized by a modest learning curve. Even though Wyeth-Ayerst engaged in a concerted and good faith effort to provide training, it is difficult to ensure competency by physicians and other providers already in practice, particularly under a voluntary program. Furthermore, the extent of involvement of US sites in the phase III and pre-introductory trials was very limited so that there was no large pool of subjects available to aid in removal training. 

Because proper insertion is critical both to minimizing local tissue complications and to facilitating uncomplicated removal, insertion by untrained providers could be especially problematic. The extent of this occurrence is unknown, but in 2 surveys of family and general practice physicians, 18% to 35% of those who offered Norplant insertions had not undergone formal training, and in one of these surveys 31% of respondents who were removing the device (which is technically more difficult) had not received formal training.137,138 These data highlight the problems that can occur as a new method moves from the research stage into market availability.

The introduction of Norplant also was unfairly clouded by the silicone-gel breast implant litigation. Although relatively few Norplant suits have claimed silicone-based injury, the apparent success of the breast implant litigation and the fact that Norplant contained silicone served as one impetus for the Norplant litigation as it became the next target for large class action filings. 

The circumstances surrounding the introduction of Norplant have likely created difficulties for future hormonal implants in the United States, and they may further affect contraceptive development in this country. Many large pharmaceutical firms have moved away from the contraceptive development area, and research into new methods of contraception has declined.139 Nevertheless, development of single-capsule or biodegradable implants with progestins that lack androgenic activity and provide contraception for shorter periods of time (1 to 2 years) may help renew interest in this field. One special variable in the United States is the litigious atmosphere that has prompted the Institute of Medicine to reiterate its recommendation that the US Congress enact a federal product liability statute that gives contraceptive manufacturers limited protection under a government standards defense.139 

Currently, Norplant retains a small niche in the array of contraceptive choices available to women in the United States as one option for those requiring long-term reversible birth control. It has lacked the overall positive impact on family planning services that has occurred in some developing countries, but it is of potential value in motivated women making an informed decision who have been dissatisfied with other contraceptive methods or experienced method failure, particularly those at high risk of unintended pregnancy, including adolescents. Norplant also is an option for most women who cannot take estrogens, and for those seeking long-term contraception as an alternative to sterilization since some women are choosing sterilization at increasingly younger ages, only to regret their decision later.

Recommendations

Because this is an informational report, there are no Recommendations.

Reports by topic

References

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