The experience of 6 million Norplant users has led to several more advanced implants. Implanon is a single-rod implant system containing a low androgenic progestin and requires 1 to 2 minutes for insertion and removal. Like other implants, Implanon prevents pregnancy by changing the character of the cervical mucus and interfering with luteal function. Unlike Norplant, though, Implanon is designed to prevent ovulation for the full duration of use. Implant contraception has several advantages over other types of contraception including high efficacy, minimal required maintenance, absence of estrogen, and rapid return of fertility after discontinuation. Implants can be a good choice for adolescents; women with hypertension, diabetes, anemia, endometriosis, or other medical problems; and women who are breast-feeding. Irregular bleeding is the most common adverse effect of implants and can be treated with several medication regimens. Preinsertion counseling, however, is the most important factor in ensuring satisfaction with implants. Unfortunately, no implant system is currently available in the United States since August 2000, but Implanon is expected to reach the U.S. market within the next 2 years.

Angiotensin II (ANG) promotes cell proliferation and angiogenesis as well as being a potent vasoconstrictor. The cellular distribution of renin, ANG and its receptors in the endometrium has yielded useful information about the possible role of the renin-angiotensin system in cyclic menstruation. In the early proliferative phase, intense ANG-like immunostaining was detected in stroma and glandular epithelia, whereas in the late secretory phase, maximal immunoreactivity was localized in the perivascular stromal cells around the endometrial blood vessels. Quantitative receptor autoradiographic studies demonstrated that the human endometrium contains predominantly ANG type 2 receptor (AT2), with a relatively low expression of ANG type 1 receptor (AT1) and a novel non-AT1/non-AT2 ANG recognition site. AT receptors displayed cyclic changes, and the highest renin concentration was detected in the late secretory phase prior to menstruation. After long-term Norplant treatment, an increase in ANG-like immunoreactivity was observed in endometrial stroma and glandular epithelia, while in hyperplastic endometrium, ANG-like immunoreactivity decreased compared with normal cyclic endometria. The pattern of ANG immunostaining in endometria from patients with irregular menstruation was markedly different from that detected in normal endometrium. Normal function of the renin-angiotensin system in endometrium may be necessary for regular cyclic menstruation, and alterations in the distribution of ANG and/or the activity of its receptors are likely to be involved in dysfunctional uterine bleeding.

OBJECTIVE

To examine the economic impact of a new implantable contraceptive, Implanon, in comparison with other available contraceptive methods.

METHODS

This was a modelling study using cost data derived from national published sources and effectiveness data from either controlled clinical trials (Implanon) or reports in the literature (other contraceptives). In the baseline analysis, Implanon was compared with 2 long term reversible contraceptives, Norplant and Mirena. Further analyses were then carried out comparing Implanon with Depo-Provera and with combined oral contraceptives.

METHODS

The study concentrated on the UK, but also made reference to several other European countries.

RESULTS

The baseline analysis showed that all 3 long term reversible contraceptives produce very good rates of return, with Implanon providing the best rate of return (both average and internal) of the 3 methods. The payback period for Implanon was calculated as 146 days, compared with 339 and 368 days for Norplant and Mirena, respectively. In terms of cost effectiveness, the cost per protected year for Implanon was 95 Pounds, compared with 146 Pounds and 168 Pounds for Norplant and Mirena, respectively. In comparison with Depo-Provera (an injectable contraceptive), Implanon was both less costly and more effective, the cost per protected year for Depo-Provera being 131 Pounds. The threshold beyond which Implanon delivers cost savings compared with combined oral contraceptives was at a failure rate of 4.9% for the combined pill.

CONCLUSIONS

Reversible long term approaches to contraception provide an effective and efficient use of healthcare resources and generate an excellent return on public investment. Implanon produces better rates of return than both Norplant and Mirena, and is also more cost effective in terms of cost per pregnancy avoided and cost per protected year than Norplant, Mirena, Depo-Provera and oral contraceptives.

This paper presents the results of a cost-benefit analysis conducted for pregnancy prevention treatment with four hormonal methods of contraception using a managed-care viewpoint. The therapies analyzed are medroxy-progesterone acetate injection (Depo-Provera), levonorgestrel subdermal implants (Norplant), progestogenonly oral tablets (Nor-QD), and combination progestogen/estrogen oral tablets (Ortho-Novum 7/7/7). Cost and benefits associated with the use of therapies are identified and analyzed based on the cost per patient-day of effective pregnancy prevention. The analysis demonstrates that all four methods have a positive net benefit, with Depo-Provera having the highest net benefit. This information can provide decision makers within a pharmacy and therapeutics committee of a managed-care organization the framework on which to base formulary decisions.

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.

The transfer of levonorgestrel (LNG) from the maternal plasma via breast milk to the infant was studied in 38 fully lactating and breast-feeding women at 4-6 weeks postpartum, for a duration of 28 days. These volunteers were provided with LNG contraceptive treatment delivered through three, different routes of drug delivery system: (i) intrauterine devices impregnated with LNG (LNG-IUD); (ii) subdermal implant (Norplant (R)-2); and (iii) minipills (LNG 30 micrograms daily). On the first day after either the LNG-IUD (n = 14 women) or Norplant (R)-2 (n = 14 women) insertion, the maternal blood and breast milk samples were collected at 2, 4 and 8 hourly intervals. This was followed by daily collection of these samples as well as infant's blood from days 2 to 4 and thereafter on days 7, 14 and 28. For infant's blood samples from LNG minipill users (n = 10 women), only a single 4-hour sample was collected on the first day and no samples were collected on days 3 and 4. The rest of the schedule for collection of maternal blood and breast milk as well as infant's blood samples were the same in minipill users as for the other two treatment groups. The study revealed a lower LNG percentage transfer from maternal sera to breast milk--11.8 +/- 2, 7 +/- 2 and 8 +/- 1 and relatively higher percentage LNG transfer from breast milk to infant's sera--75 +/- 17, 68 +/- 20 and 32 +/- 3, in LNG-IUD, Norplant (R)-2 and minipill users, respectively. Therefore, LNG contraceptive steroid is transferred into the infant's circulation, the biological significance of which remains to be established.

BACKGROUND

Despite their high effectiveness, progestin-only contraceptives are considered less than ideal by the many women who experience irregular vaginal bleeding when using them. Current treatments to control these bleeding problems are not sufficiently effective.

OBJECTIVE

We evaluated preventive and therapeutic approaches to normalise bleeding irregularities associated with the use of progestin-only contraceptives.

METHODS

Literature was identified through database searches, reference lists, organisations and individuals, covering the period until May-June 2012.

METHODS

Trials with random or systematic allocation, testing interventions for the prevention or treatment of bleeding irregularities associated with the use of progestin-only contraceptives were eligible.

METHODS

Results are expressed as relative risks (RR) with 95% confidence interval (CI) for categorical data and as weighted mean difference (WMD) with 95% CI for continuous data. When we encountered heterogeneity (visual or statistical) we used the random-effects model (quantitative) or did not produce a summary estimate (qualitative).

RESULTS

Thirty-three randomised controlled trials enrolling 3677 participants were included. Two thirds of the trials were determined to reflect low to moderate risk of bias.Estrogen treatments reduced the number of days of an ongoing bleeding episode in DMPA and Norplant users. However, treatment frequently led to more discontinuation due to gastrointestinal upset.Combinations of oral ethinyl estradiol and levonorgestrel improved bleeding patterns in Norplant users, but method discontinuation rates were unchanged. One trial reported successful use of combined oral contraceptives in treating amenorrhea among DMPA users.Norplant users, but not Implanon users, administered the anti-progestin mifepristone reported fewer days of bleeding during treatment than those given placebo. Mifepristone used monthly by new Norplant acceptors reduced bleeding, when compared to placebo.A variety of NSAIDS have been evaluated for their ability to treat abnormal bleeding, with mixed results.Norplant users receiving SERM (tamoxifen) had less unacceptable bleeding after treatment and were more likely to continue using Norplant than those receiving placebo.Tranexamic acid, mifepristone combined with an estrogen and doxycycline were more effective than placebo in terminating an episode of bleeding in women using progestin-only contraceptives, according to three small studies.

CONCLUSIONS

Some women may benefit from the interventions described, particularly with cessation of current bleeding. Several regimens offer promise in regulating bleeding, but findings need to be reproduced in larger trials. The results of this review do not support routine clinical use of any of the regimens included in the trials, particularly for long-term effect.

Ever since natural sex hormones have been identified, their structure defined and their synthesis achieved, it became clear that their circulating half-life was too short to allow use in therapy. One of the modalities most thoroughly investigated to prolong their duration of action is to embed them in a polymeric matrix and administer them subcutaneously. Research and development activities of devices to be inserted under the skin have focused upon two modalities: the first utilizes the so-called nonbiodegradable devices, in which the matrix is fixed and the drug is made available through diffusion. In the second, biodegradable devices, the matrix dissolves during the process and both the active compound and the matrix components reach the circulation. Although a number of biodegradable systems have been investigated in the form of polymeric rod or micropellets, so far no system has reached the marketplace. Several matrices have been evaluated: poly(ortho esters), (polylactic-polyglycolic acid)co-polymers, poly-(epsilon-caprolactone). In the case of nonbiodegradable systems, several have been in widespread use for years. The first such system, Norplant 1, consists of six capsules delivering levonorgestrel and lasts a minimum of 5 years; the second, called Norplant 2 (Jadelle), consists of only two rods delivering the same amount of steroid of the first system, for the same duration of time. A third system already on the market is made up of a single rod releasing etonogestrel, the active metabolite of desogestrel, with duration of action of 3 years. Additional systems are still at the premarket stage. Subcutaneous implants have several obvious advantages, first and foremost their duration of action that can extend to at least 5 years, making them especially suitable for family-planning programs in developing countries; in addition, they are user- independent, again a positive feature in certain settings. Among the disadvantages, is a relatively complex insertion procedure that, for older systems, required ad hoc trained personnel and a small incision, clearly a disincentive. Newer devices, however, require a much simpler insertion procedure. Extracting systems is also complex and if a woman is lost to follow-up, implants will remain in the subcutaneous tissue forever.

The Norplant System of subdermally-implanted levonorgestrel-containing capsules is the most effective reversible contraceptive option available to women today. Patients' acceptance of the System is high and crosses cultural, social, and economic boundaries. As more women become aware of the Norplant System it is increasingly important for all primary health care providers to be knowledgeable and proficient in the procedures for insertion and removal. Both procedures are short, in-office procedures that are straight-forward and easy to master. This article examines the Norplant System, with emphasis on the removal procedure, and offers tips and techniques for nurse practitioners planning to add Norplant-related skills to their repertoire. Topics covered include a brief review of the history and methods of action of Norplant, the importance of patient counseling, the insertion procedure, the removal procedure, and tips for handling nonstandard removal situations.

In this prospective randomized clinical trial, two long-term contraceptive implants were studied with respect to hemostasis and liver function in 86 healthy young women. The two implants used were Implanon, containing the progestagen etonogestrel (the biologically active metabolite of desogestrel) and Norplant, the implant containing the progestagen levonorgestrel. The results of the trial showed that both implants had similar small effects on the hemostatic system that are not suggestive of a tendency towards thrombosis. The effect on liver function was characterized by increases in total bilirubin and gamma-glutamyl transferase and decreases in alanine aminotransferase and aspartate aminotransferase.

The objective of this study was to assess the possible differences in effects of Implanon (etonogestrel 68 mg, single-rod) and Norplant (levonorgestrel 36 mg, six capsules) implants on serum lipids over 2 years of use. In this 2-year open randomized study of 80 implant acceptors, selected serum lipids were tested before implant insertion and at 6, 12 and 24 months after implant insertion. The lipid parameters evaluated were: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, apolipoprotein A-I and apolipoprotein B. During the 2 years, the serum lipid pattern in the Implanon users was not significantly different from that of the Norplant users. There was slight decrease in HDL-C levels in both the groups but there were no significant changes in the HDL/TC ratio and the HDL/LDL ratio. Although it was statistically significant, the magnitude of decrease in HDL-C from preinsertion levels in Implanon users was only 5.8% at the end of 2 years.

The metabolic impact of progestin-only contraceptives is less than that of combined oral contraceptives. Subdermal contraceptive implant systems that provide a sustained release of low levels of progestins are now becoming widely available. This review evaluates the metabolic effects of currently available products that release the progestins levonorgestrel (Norplant, Jadelle, and their Chinese equivalents); etonogestrel (Implanon); nomegestrol acetate (Uniplant); and Nestorone, formally called ST-1435 (Nestorone implant/Elcometrine). Data on liver, kidney, and renal function; carbohydrates and insulin release; hemostasis; blood pressure; and lipids are considered. The metabolic effects reported for these methods as a whole were minimal. Any changes were generally within the normal range for the populations studied and, therefore, are unlikely to be of clinical significance. However, all published studies have been conducted in healthy populations of women. To inform clinical practice, the field would be well served to have additional empiric data from well-designed, well-implemented, and well-reported trials in women who are deemed to be at elevated risk for certain diseases including cardiovascular disease and diabetes.

The effects of combined oral contraceptives (OC), depot medroxyprogesterone acetate injections (DMPA), levonorgestrel subdermal implant (Norplant), copper-containing intrauterine devices (copper IUD), and Chinese stainless steel ring IUD on hemoglobin and ferritin were studied in 18-40-year-old, nonpregnant, and nonlactating women in seven countries (Bangladesh, Chile, China, the Dominican Republic, Pakistan, Thailand, and Tunisia). Data from 2507 women were analyzed. The study had a cross-sectional component in which 1295 current users of the contraceptive methods were compared with 1212 women initiating use of contraceptives. The results of this component showed that the current users of hormonal contraceptive methods generally had higher hemoglobin and ferritin levels than the noncontraceptors. The differences between women using hormonal contraceptive and noncontraceptors in mean values for hemoglobin varied between 3 and 6 g/L and for ferritin between 2 and 18 g/L. The current users of copper IUD had higher hemoglobin levels (difference in mean levels of 3 g/L), but lower ferritin levels (difference of 10 g/L) than noncontraceptors. Current use of the stainless steel ring had an adverse effect on both hemoglobin and ferritin. In a longitudinal component of the study, 285 anemic women (hemoglobin between 80 and 120 g/L at the time of initiation of contraception)--a subgroup of the cross-sectional component--were followed-up at 3, 6, and 12 months after initiation. In this component, significant mean increases of hemoglobin at 12 months were observed among the users of oral contraceptives and DMPA, but not among users of copper or stainless steel ring IUD. It is concluded that hemoglobin and ferritin levels are influenced by the use of contraceptives and that the hormonal contraceptives included in the present study have a beneficial effect on these parameters. The effects of copper IUD on hemoglobin and ferritin should be studied further.

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

Although new contraceptive technology has the potential for providing women with expanded options for fertility control, the historical record of international family planning shows that, in practice, introduction of new methods has not always broadened reproductive choice. Using the example of introduction of intrauterine devices into the Indian family planning program in the 1960s, we show that an exclusive focus on the technology itself is problematic and argue that methodologies are needed that relate introduction of new methods to user needs and program capacities. We summarize key findings from the Indonesian experience with Norplant introduction. Although an effort was made to address problems with previous approaches, major deficiencies in both the technical and interpersonal dimensions of care arose when the implants were made broadly available within the program. We subsequently present a methodology for contraceptive introduction developed by the World Health Organization. This methodology emphasizes the social and institutional context in which technology is used and suggests a participatory and research-based approach to program and policy development. We illustrate results from this new approach in its implementation in Vietnam and suggest areas for further evaluation.

Realizing the promise of long-acting contraceptives depends on continuing efforts to distinguish appropriate from inappropriate policies and practices. The current debates concerning Norplant and other long-term methods generally have based ethical judgment on too slim a reed. It is insufficient and overly divisive to limit the tools of analysis to questions of freedom and coercion. A richer perspective is needed. We have sketched out an alternative approach that rests on a close, case-by-case analysis attentive to the social dimension and consequences of contraceptive decisionmaking, as well as to the individual interests at stake. The approach also takes special note of the need for access to long-acting contraceptive, the possibility for mistaken nonuse as well as mistaken use, and our country's past and present biases and power imbalances. We do not claim that this method will make judgments about justifiable or unjustifiable influence easy or automatic. However, it should prove adept at underscoring the factors that require particular scrutiny. Perhaps more importantly, the approach highlights that influences for the use of long-acting contraceptives ought to be judged, not merely dismissed.

Our objective in this systematic review was to evaluate evidence regarding controversial issues in the clinical management of women using injectable and implantable contraceptives. We searched MEDLINE and EMBASE for reports of primary research, published from 1966 through April 2005 in peer-reviewed journals, related to the initiation of combined or progestogen-only injectables and contraceptive implants, the effects of late contraceptive injections or the duration of levonorgestrel implant effectiveness. Results of the studies we reviewed showed that initiating injectable and implantable contraceptives through day 7 of the menstrual cycle suppresses follicular activity. Time to ovulation after study participants discontinued using injectables varied widely: from 4 to 8 weeks after the last administration of combined injectables, from 15 to 49 weeks after the last injection of depot medroxyprogesterone acetate and from 5 to 19 weeks after the last injection of norethisterone enanthate. Norplant implants left in place for up to seven completed years remained effective among women who weighed <70 kg at the time of implant insertion, but their effectiveness decreased among women weighing>>or=70 kg.

Norplant, the five-year subdermal contraceptive system, is the first implantable contraceptive method approved for general use in the United States. We describe the preliminary experiences of 246 U.S. women who accepted Norplant between April, 1991 and September, 1991. Norplant was well accepted among this diverse general population. Intensive counselling about side effects, especially menstrual changes, is crucial for patient satisfaction. Although 48% of acceptors experienced menstrual cycle changes and 70% experienced at least one side effect, phone calls and unscheduled visits for problems were infrequent. Adequate counselling about side effects obviates the need for a routine follow-up visit one month after insertion.

The effectiveness of Norplant implants over a seven year period of continuous use was studied in a multicenter trial. Pregnancy rates were 0.4 per 100 in both year six and year seven. More than 3,600 women completed 6 years and more than 2,400 women completed 7 years. Pregnancy rates increased with weight (p < .05) and decreased with age, but in years 6 and 7 combined, the pregnancy rate neither reached nor exceeded 1 per 100 woman years in any 5 year age group or in any 10 kg weight group.

OBJECTIVE

To identify characteristics of patients 18 years of age and younger who would and would not consider using levonorgestrel implants (Norplant) for contraception and to isolate potential barriers to its use.

METHODS

Survey of 323 adolescents attending family planning or obstetrics clinics between April 29 and October 27, 1992. For purposes of analyses, patients were stratified by their willingness to consider using Norplant. Statements about Norplant that differentiated between groups were considered significant barriers. Additional analyses were conducted for the sample, stratified by pregnancy status, race and ethnicity, parity, and Norplant class attendance.

RESULTS

Sixty-four percent of participants stated that they would be willing to consider using Norplant. These adolescents were significantly older, were more likely to already have given birth or have had abortions, planned to delay (additional) childbearing for 5 or more years, aspired to receive college educations, and reported lower annual household incomes than did adolescents unwilling to consider using the device. Identified barriers to Norplant use included misinformation, perceived advantages, physical aversions, perceived efficacy, fertility concerns, social influences, and concerns about safety and side effects.

CONCLUSIONS

Misperceptions and concerns about safety and side effects will prevent many adolescents from using Norplant. Recent negative publicity surrounding its use will intensify this problem. Health care providers must work to remove these barriers so that sexually active adolescents can make informed decisions about contraceptives.