Contraceptive implants are a good choice for women of reproductive age who are sexually active and desire long-term, continuous contraception. Implants should be considered for women who:

Implant use is contraindicated in women who have:

Based on clinical judgment and appropriate medical management, Implants MAY BE USED by women with a history of or current diagnosis of the following conditions:

Implants are not contraindicated in the following situations, but other methods are preferable:

Carbamazepine (Tegretol)

Felbamate

Lamotrigine

Nevirapine

Oxcarbazepine

Phenobarbital

Phenytoin (Dilantin)

Primidone (Mysoline)

Rifabutin

Rifampicin (Rifampin)

St. John’s wort

Topiramate

Vigabatrin

Possibly valproic acid, ethosuximide, griseofulvin, and troglitazone

We do not recommend the use of implants with any of the previously listed drugs because of a likely increased risk of pregnancy due to lower blood levels of the progestin.^14,15

The release rate of the contraceptive implants is determined by total surface area and the density of the implant in which the progestin is contained. The progestin diffuses from the implant into the surrounding tissues where it is absorbed by the circulatory system and distributed systemically, avoiding an initial high level in the circulation as with oral or injected steroids. Within 8 h after insertion of Implanon, plasma concentrations of etonogestrel are about 300 ng/mL, high enough to prevent ovulation.¹⁶ A study of cervical mucus changes with Norplant indicates that a backup method should be used for 3 days after insertion of Norplant or Jadelle; this is not necessary when Implanon is inserted as directed.^17,18 Progestin concentrations are much more variable with Norplant and Jadelle than with Implanon.¹⁶

The Implanon rod releases 60 μg of etonogestrel per 24 h at 3 months of use. This rate declines gradually to 40-50 μg daily by 12 months and 30 μg/day by 2 years of use. The 85 mg of hormone released by Norplant or the 100 mg released by Jadelle during the first few months of use is about equivalent to the daily dose of levonorgestrel delivered by the progestin-only, minipill oral contraceptive, and 25-50% of the dose delivered by lowdose combined oral contraceptives. After 6 months of use, daily levonorgestrel concentrations are about 0.35 ng/mL; at 2.5 years, the levels decrease to 0.25-0.35 ng/mL. Until the 8-year mark, mean levels remain above 0.25 ng/mL.¹⁹ Mean plasma concentrations below 0.2 ng/mL are associated with increased pregnancy rates for Norplant (lower levels are more likely in heavier women).

Body weight affects the circulating levels of levonorgestrel; the greater the weight of the user, the lower the levonorgestrel concentrations at any time during Norplant or Jadelle use. The greatest decrease over time occurs in women weighing more than 70 kg (154 lb), but even for heavy women, the release rate is high enough to prevent pregnancy at least as reliably as oral contraceptives. In Implanon users, etonogestrel concentrations are affected very little by body weight, and failure rates did not increase with increasing body weight in the small numbers of overweight women in the clinical trials.²⁰ Although the data with overweight women are limited, it is likely that Implanon is a good contraceptive choice for obese women.

Levonorgestrel levels can also be affected by the circulating levels of sex hormone-binding globulin (SHBG). Levonorgestrel has a higher affinity for SHBG than does etonogestrel. In the week after Norplant or Jadelle insertion, SHBG levels decline rapidly and then return to approximately half of preinsertion levels by 1 year of use. This effect on SHBG is not uniform and may account for some of the individual variations in circulating progestin concentrations.²¹

Implants are highly effective contraceptives. There are three probable modes of action, which are similar to those attributed to the contraceptive effect of the progestin-only minipills, but because daily dosing is not required, implants are more effective than oral methods.

Implants are a safe, highly effective, continuous method of contraception that requires little user effort and, unlike long-acting injectable contraception, is rapidly reversible. Because this is a progestin-only method, it can be used by women who have contraindications for the use of estrogen-containing contraceptives. The sustained release of low doses of progestin avoids the high initial dose delivered by injectables and the daily hormone surge associated with oral contraceptives. Implants are an excellent choice for a breastfeeding woman and can be inserted immediately postpartum. There are no effects on breast milk quality or quantity, and infants grow normally.^27,28,29 and ³⁰ Another advantage of the implant method is that it allows women to plan their pregnancies precisely; return of fertility occurs within a few weeks, in contrast to the 6- to 18-month delay in ovulation that can follow depotmedroxyprogesterone acetate injections.^16,31,32 and ³³

One of the major advantages of sustained-release methods is the high degree of efficacy, nearly equivalent to the theoretical effectiveness. In couples for whom elective abortion is unacceptable in the event of an unplanned pregnancy, the high efficacy rate is especially important. There are no forgotten pills, broken condoms, lost diaphragms, or missed injections. For women who are at high risk of medical complications should they become pregnant, sustained-release implants present a significant safety advantage. Users should be reassured that implant use has not been associated with changes in carbohydrate or lipid metabolism, coagulation, liver or kidney function, or immunoglobulin levels. Because many women wanting implants will have had negative experiences with other contraceptives, it is important that the differences between this method and previous methods be explained.

Exposure of endometriosis to progestin-only contraceptive methods is an effective method to manage the pain associated with this condition. Implanon, depot-medroxyprogesterone acetate, and the levonorgestrel-containing intrauterine device have all been reported to reduce endometriosis pain.^34,35,36,37 and ³⁸

There are some disadvantages associated with the use of the implant systems. Implants cause disruption of bleeding patterns, especially during the first year of use, and some women or their partners find these changes unacceptable.⁴ Endogenous estrogen is nearly normal, and unlike the estrogen-progestin contraceptives, progestin is not regularly withdrawn to allow endometrial sloughing. Consequently, the endometrium sheds at unpredictable intervals.

The implants must be inserted and removed in a surgical procedure performed by trained personnel. Women cannot initiate or discontinue the method without the assistance of a clinician. The incidence of complicated removals is approximately 5% for Norplant or Jadelle and lower for Implanon, an incidence that can be best minimized by good training and careful insertion.^39,40 The implants can be visible under the skin. This sign of the use of contraception may be unacceptable for some women and for some partners.⁴

Implants do not provide protection against sexually transmitted infections (STIs) such as herpes, human papillomavirus, HIV, gonorrhea, or chlamydia. Although users may be less likely to use a second method because of the high contraceptive efficacy,⁴¹ users at risk for STIs must use condoms as a second method to prevent infection.

Because the insertion and removal of implants require minor surgical procedures, initiation and discontinuation costs are higher than with oral contraceptives or barrier methods. The cost of implants plus fees for insertion total an amount that may seem high to patients unless they compare it with the total cost of using other methods for up to 5 years.⁴² Nevertheless, short-term use is expensive compared with the relatively low initial costs of other reversible methods, and most women cannot be expected to use long-acting methods for their full duration of action.

Cultural factors can influence the acceptability of menstrual changes. Some cultures restrict a woman from participating in religious activity, household activities, or sexual intercourse while menstruating. All users must be aware of the possible menstrual changes. It is important to stress that all of the menstrual changes are expected, that they do not cause or represent illness, and that most women revert back to a more normal pattern with increasing duration of use.

Insertion and removal of implants will be a new experience for most women. As with any new experience, women will approach it with varying degrees of apprehension and anxiety. In reality, most patients are able to watch in comfort as implants are inserted or removed. Women should be told that the incisions used for the procedures are very small and heal quickly, leaving small scars that are usually difficult to see because of their location and size.

We encourage prospective users to see and touch implants. Women can be reassured that the implants will not be damaged or move if the skin above them is accidentally injured. Normal activity cannot damage or displace the implants. Most women become unaware of their presence. A few women report sensing the implants if they have been touched or manipulated for a prolonged period of time, or after vigorous exercise. The implants are more visible in slender women with good muscle tone. Darker-skinned users may notice further darkening of the skin directly over the implants; this resolves after removal.

Contraceptive implants provide highly effective birth control. In 2-year or 3-year studies in 11 international clinical trials of 942 women using Implanon, no pregnancies occurred.²⁰
In studies of Norplant conducted in 11 countries, totaling 12,133 woman-years of use, the pregnancy rate was 0.2 pregnancies per 100 woman-years of use.^15,31 All but one of the pregnancies that occurred during the Norplant evaluation were present at the time of implant insertion. If these luteal phase insertions are excluded from analysis, the first-year pregnancy rate was 0.01 per 100 woman-years. In adolescents, Norplant implants provide better protection against unwanted pregnancy, compared with oral contraceptives, and an important factor is the better continuation rate with Norplant.^41,43,44

There are no weight restrictions for Norplant or Jadelle users, but heavier women (more than 70 kg) may experience slightly higher pregnancy rates in the later years of use compared with lighter women. Even in the later years, however, pregnancy rates for heavier women using Norplant are lower than with oral contraception. The differences in pregnancy rates by weight are probably due to the dilutional effect of larger body size on the low, sustained serum levels of levonorgestrel. Heavier women should not rely on Norplant or Jadelle beyond the 5-year limit. For slender women the duration of efficacy extends well past the fifth year of use. In some extended trials, no pregnancies have occurred into the seventh year. Data are not available regarding the effect of body weight on the efficacy of Implanon, but unlike Norplant and Jadelle, progestin levels are not significantly lower in heavier women.

The contraceptive efficacy of Implanon surpasses that of Norplant and sterilization.² Only a rare pregnancy occurs, resulting in a Pearl Index of about 0.01.^23,47 In over 70,000 cycles, no pregnancies were recorded because of total inhibition of ovulation until ovulations were observed in the last 6 months of the 3-year period.^23,48 Post-marketing surveillance of pregnancies in Australia, where nearly one-quarter of contraceptors relied on Implanon in 2004, revealed that of 218 pregnancies, only 13 could possibly have been failures of the method.⁴⁹ In Australia and the Netherlands, pregnancies commonly were the consequence of poor insertion technique, especially allowing the implant to fall unnoticed to the floor.
Implants have an immediate contraceptive effect when inserted within the first 7 days of a menstrual cycle, but when insertion is after day 7, a backup method of contraception is necessary for at least 3 days.⁵⁰

The ectopic pregnancy rate during Norplant use is 0.28 per 1,000 woman-years.¹⁵ Although the risk of developing an ectopic pregnancy during use of Norplant is low, when pregnancy does occur, ectopic pregnancy should be suspected because approximately 30% of Norplant pregnancies are ectopic. Because Implanon is more effective in inhibiting ovulation, we would expect the risk of ectopic pregnancy to be considerably less than that associated with Norplant.

Menstrual bleeding patterns are highly variable among users of implant contraception. With levonorgestrel implants, some alteration of menstrual patterns will occur during the first year of use in approximately 80% of users, later decreasing to about 40%, and by the fifth year, to about 33%.^53,54 The changes include alterations in the interval between bleeding, the duration and volume of menstrual flow, and spotting. Oligomenorrhea and amenorrhea also occur but are less common, less than 10% after the first year and diminishing thereafter. Irregular and prolonged bleeding usually occurs during the first year. Although bleeding problems occur much less frequently after the second year, they can occur at any time.^54,55 Studies of the endometrium in Norplant users experiencing abnormal bleeding indicate the presence of enlarged venous sinusoids (fragile vessels) and a reduction in the expression of a protein factor (perivascular stromal cell tissue factor) involved in the initiation of hemostasis.⁵⁶ Within weeks after insertion, the density of endometrial small blood vessels increases and the endometrium regresses to an atrophic state.⁵⁷ It is believed that bleeding is a consequence of rapid endometrial regression and that the apparent increase in the number of blood vessels may reflect increased tortuosity accompanying the atrophic regression.

Implanon alters menstrual patterns, but amenorrhea occurs more often (21% of users in the first year, 30-40% after 1 year) than with Norplant.^11,13 A single Implanon rod completely suppresses ovulation for 2.5 years, and, therefore, menses do not become more regular after the first 2 years as with Norplant. After 2 years, ovulation occurs in about half of the menstrual cycles. Bleeding is lighter and less frequent among Implanon users because more profound ovarian suppression results in less follicular estrogen production and less endometrial stimulation, nevertheless irregular bleeding continues to be a a major reason for discontinuation.^13,58

Despite an increase in the number of spotting and bleeding days over preinsertion menstrual patterns, hemoglobin concentrations rise in Norplant users because of a decrease in the average amount of menstrual blood loss.^59,60,61 and ⁶² Implanon likewise does not cause anemia.¹¹

Implant users who can no longer tolerate prolonged bleeding will benefit from a short course of oral estrogen: conjugated estrogens, 1.25 mg, or estradiol, 2 mg, administered daily for 7 days.⁶³ A therapeutic dose of one of the prostaglandin inhibitors given during the
bleeding will help to diminish flow, but estrogen is the most effective treatment.^64,65 Another approach is to administer an estrogen-progestin oral contraceptive for 1-3 months.⁶⁶

Although implants are very effective, pregnancy must be considered in women reporting amenorrhea who had been ovulating previously, as evidenced by regular menses prior to an episode of amenorrhea. A sensitive urine pregnancy test should be obtained. Women who remain amenorrheic throughout their use of implants are unlikely to become pregnant.⁵⁴ It is important to explain to patients the mechanism of the amenorrhea: the local progestational effect causing decidualization and atrophy.

Exposure to the sustained, low doses of progestin delivered by the implants is not associated with significant metabolic changes. Studies of liver function,^10,67,68 blood coagulation,^10,69,70 and ⁷¹ immunoglobulin levels,^72,73 serum cortisol levels,⁷⁴ and blood chemistries^68,72 have failed to detect changes outside of normal ranges in Norplant users.

No major impact on the lipoprotein profile can be demonstrated with Norplant.^67,75,76 Minor changes are transient, and, with prolonged duration of use, lipoproteins return to preinsertion levels. Long-term exposure to the low dose of levonorgestrel released by Norplant is unlikely to affect users’ risk of atherogenesis, just as prolonged exposure to combined oral contraception has not. There are no clinically important effects on carbohydrate metabolism.^72,77 77^,78 No effect on insulin sensitivity can be detected.⁷⁹ In a cohort study of 5 years’ duration, no increase was observed in diabetes mellitus, depression, lupus erythematosus, cardiovascular diseases—in fact there was no increase in serious morbidity.⁸⁰

There are no significant metabolic differences comparing Implanon and Norplant.⁸¹ Neither implant system has important clinical effects on the lipoprotein profile, carbohydrate metabolism, thyroid and adrenal function, liver function tests, or the clotting mechanism.^10,58,82 Implant contraception is a good choice for a woman at risk for estrogen-associated thromboembolism. Because of the lower androgenic characteristic of etonogestrel, Implanon does not cause a decrease in the levels of sex hormone-binding globulin.⁸²

Measurements of bone density in young women reveal that Implanon and Norplant do not affect the teenage gain in bone; similar gains in bone were recorded in implant users and control subjects.^83,84 In older women, an increase in forearm, spine, and femur bone density has been documented after 6 and 12 months of Norplant use.^85,86 An international crosssection study reported a small loss in bone density with Norplant that was rapidly regained after discontinuation.⁸⁷

A slight increase in gallbladder disease has been noted in Norplant users.^2,88 This is at best just a word of caution because the association is weak and may reflect preexisting disease, and there is no apparent biologic mechanism.

Circulating levels of progestin become too low to measure within 48 h after removal of implants. Most women resume normal ovulatory cycles during the first month after removal. The pregnancy rates during the first year after removal are comparable with those of women not using contraceptive methods and trying to become pregnant. There are no long-term effects on future fertility nor are there any effects on sex ratios, rates of ectopic pregnancy, spontaneous miscarriage, stillbirth, or congenital malformations.^15,31
The return of fertility after implant removal is prompt, and pregnancy outcomes are within normal limits. The rate and outcome of subsequent pregnancies are not influenced by duration of use.

For women who are spacing their pregnancies, the difference between implants and depot-medroxyprogesterone acetate in the timing of the return to fertility can be critical. Implants allow precise timing of pregnancy because the return of ovulation after removal is prompt. Etonogestrel serum levels are undetectable within one week after removal of Implanon, and ovulation can be expected in the first month after discontinuation.⁹ Depotmedroxyprogesterone acetate, on the other hand, can cause up to 18 months’ delay in return to fertility. By that time, 90% of users of either method will have ovulated, but in the first several months, the difference is dramatic. By 3 months after removal, half of implant users will have ovulated, but 10 months must elapse before half of depot-medroxyprogesterone acetate users are ovulatory.

The occurrence of serious side effects is very rare, no different in incidence than that observed in the general population. In addition to the menstrual changes, levonorgestrel implant users have reported the following side effects: headache, acne, weight change, mastalgia, hyperpigmentation over the implants, hirsutism, depression, mood changes, anxiety, nervousness, ovarian cyst formation, and galactorrhea.^{15,31,53,55,89}

It is difficult, of course, to be certain which of these effects were actually caused by the levonorgestrel. For example, careful study fails to reveal a relationship between Norplant use and depressive symptoms.⁹⁰ Although most of these side effects are minor in nature, they can cause patients to discontinue the method. Patients often find common side effects tolerable after assurance that they do not represent a health hazard.⁴ Many complaints respond to reassurance; others can be treated with simple therapies. The most common side effect experienced by users is headache (16% of Implanon users); approximately 20% of women who discontinue use do so because of headache.^4,20,89

Stroke, thrombotic thrombocytopenic purpura, thrombocytopenia, and pseudotumor cerebri have been reported with Norplant.⁹¹ However, it is by no means established that the incidence of these problems is increased, and there is little reason to suspect a cause-andeffect relationship. In the follow-up study conducted by the World Health Organization in eight countries, no significant excess of cardiovascular events or malignant disease was observed.⁹²

A large 5-year follow-up study in developing countries confirmed the low pregnancy rates associated with Norplant, 0.23 per 100 woman-years for intrauterine pregnancy and 0.03 per 100 woman-years for ectopic pregnancy.⁹² When the women using Norplant were compared with women using nonhormonal methods of contraception and to the expected population rates, there was no excess of cancers, connective tissue diseases, or cardiovascular events. Importantly, the complaints of headache and mood disturbances (including anxiety and depression) were similar to those reported by women using oral contraceptives, although higher than for women using IUDs.

The usual personal and family medical history and physical examination should concentrate on factors that might contraindicate use of the various contraceptive options. If a patient elects to use contraceptive implants, a detailed description of the method, including effectiveness, side effects, risks, benefits, as well as insertion and removal procedures, should be provided. Before insertion, the patient is asked to read and sign a written consent for the surgical placement of the implants. The consent reviews the potential complications of the procedure that include reaction to the local anesthetic, infection, expulsion of the implants, superficial phlebitis, bruising, and the possibility of a subsequent difficult removal.

Insertion can be performed at any time during the menstrual cycle as long as pregnancy can be ruled out. If the patient’s last menstrual period was abnormal, if she has recently had sexual intercourse without contraception, or if there are reasons to suspect pregnancy, a sensitive urine pregnancy test is a wise precaution. Based on cervical mucus changes, a backup method need be used no more than 3 days after insertion.¹⁸ Implants can be inserted immediately postpartum but certainly should be initiated no later than the third postpartum week in non-breastfeeding women and the third postpartum month in breastfeeding women. Acne and headache are less common in women who receive Norplant immediately postpartum, and there is no difference in postpregnancy weight loss compared with women who receive it 4-6 weeks later.⁹⁷

Patients should be questioned about allergies to local anesthetics, antiseptic solutions, and tape. A discussion about the technique of insertion and anticipated sensations is an important part of preparing the patient for the experience. All patients approach insertion with some degree of apprehension that can be decreased by detailed explanations and preparation.^98,99

Selection of the site for placement of implants is based on both functional and aesthetic factors. Various sites (the upper leg, forearm, and upper arm) have been used in clinical trials. The nondominant, upper, inner arm is the best site. This area is easily accessible to the clinician with minimal exposure of the patient. It is well protected during most normal activities. It is not highly visible, and migration of the implants from this site has not been documented. The site of placement does not affect circulating progestin levels. Careful implant insertion is the key to trouble-free removal.

Implanon offers important insertion advantages compared with Norplant.¹⁰⁰ Of course, only one rod simplifies and shortens both insertion and removal. In addition, a pre-loaded applicator is provided that facilitates placement. If necessary, Implanon can usually be visualized by ultrasonography.¹⁰¹ However, if a nonpalpable rod is not visible on ultrasonography, definitive localization is best achieved with magnetic resonance imaging (MRI).¹⁰² Removal of the Implanon rod uses the “fingers alone” technique with a 2 mm incision.¹⁰³ Insertion complications (mainly deep insertions) are rare, and removal complications (difficulty finding the implant or a broken implant) occur at a far greater lower frequency compared with Norplant.^1,100

Insertion is carried out under local anesthesia in the office or clinic by someone, usually a physician or nurse practitioner, trained in the technique described here.¹⁰⁴ The procedure takes 5-10 min for a six implant system, and 2-3 min for a single implant.¹⁰⁵

Potential complications include infection, hematoma formation, local irritation or rash over the implants, expulsion of the implant, and allergic reactions to adhesives of the dressing. Implanon can migrate a short distance (less than 2 cm) over time.¹⁰⁸ The incidence of complications is minimized by clinician training and experience, and the use of strict aseptic technique. Post-insertion pregnancies in Australia and the Netherlands were commonly due to a failure to insert the implant (allowing the implant to fall out prior to insertion). The clinician must make sure the implant is visualized in the trocar prior to insertion and after insertion is palpable under the skin.

Although implant removal is an office procedure requiring only a small amount of local anesthesia and a few simple instruments, instruction and practice are necessary.¹⁰⁷
Practicing on a model arm after viewing an instructional video makes first removals faster and less uncomfortable for both clinician and patient. A removal kit with a model arm, a manual, and compact disc illustrating the technique is available at no charge from Schering-Plough at 877-467-5266. As for insertion, the patient should read and sign an informed consent to be filed in her medical record. We recommend that the patient be given a copy.