• Summary
• Credits

1. The Long Road of Contraceptive Development
2. Vaginal Rings
3. Transdermal Contraception
4. Contraceptive Implants
• New Formulations with Fewer Rods
• Side Effects
5. Combined Injectables
6. Condoms
7. Fertility Awareness-Based Methods
8. Oral Contraceptives
9. Intrauterine Devices
10. Transcervical Female Sterilization
11. Male Hormonal Contraception
12. Bibliography
13. Web Supplements

• Clinical trials assess effectiveness and safety of new contraceptives
• New low-dose DMPA formulation
• More long-term choices for men

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• POPLINE

Contraceptive Implants

New Contraceptive Implants Description: One or two progestin-releasing rods inserted just under the skin. Stage of development: One entering phase III clinical trials and two being marketed worldwide. Effectiveness: 0.3 to 1.1 pregnancies per 100 women in the first year of use as typically used. How they work: Progestin released under the skin thickens the cervical mucus, prevents ovulation in many cycles, and suppresses endometrial growth. What’s new? Fewer rods than Norplant implants and therefore easier and quicker to insert and remove.

New research on contraceptive implants has focused on reducing the number of rods or capsules by using different progestins, minimizing side effects, particularly bleeding disturbances, and assuring that implants are safe for use while breastfeeding (221). Women around the world use Norplant^® implants, the first implant available, approved by the US FDA in 1990. Norplant implants employ six capsules to deliver the progestin levonorgestrel. They provide excellent contraceptive protection but in some countries also have high discontinuation rates due to bleeding disturbances. Such bleeding changes are the most common side effect of implant use and the reason women give most often for discontinuing use (87, 193).

The newer implants are similar to Norplant implants but offer several improvements. The new implants consist of one or two rods or capsules. Like Norplant implants, they are inserted just under the skin of the upper arm to deliver progestins into the bloodstream. Most use rods rather than capsules. Rods differ from capsules in that they are filled with a mixture of steroid crystals and polymer. Capsules, on the other hand, are hollow polymer tubes filled with free steroid crystals (62).

Two of the new implants—Jadelle^® and Implanon^®—are approved in many countries, while the other new formulation, Nestorone, is not yet on the market. The new implants have been slow to become available. There are several reasons: They are expensive to develop and market, their initial expense is too high for many family planning programs, and they require provider training in techniques of insertion and removal.

Also, for some women the advantages of implants may not be much greater than those of other methods such as the IUD, which is longer lasting and less expensive. Nevertheless, experts and pharmaceutical companies expect that over the next decade, as more countries register the new implants, they will replace Norplant implants and will be offered by some family planning programs that have not provided implants previously (106, 221).

New implant systems with fewer capsules or rods make insertion and removal much easier and produce fewer complications and less discomfort for users compared with Norplant’s six capsules (150, 218). The newer implants are inserted using a specially designed preloaded applicator that eliminates the need for a separate incision (216).

Most insertions of Jadelle take less than five minutes (218, 222). Rates of complications and removal are about half those for Norplant implants (216). For trained providers using a preloaded disposable applicator, Implanon insertion takes less than one minute (254).

New implants deliver the progestin levonorgestrel (Jadelle and Chinese No. 2), etonogestrel (Implanon), or ST-1435 (Elcometrine and Nestorone implant). Implants work primarily by thickening cervical mucus so that it is impenetrable to sperm, preventing ovulation in many cycles, and supressing endometrial growth (30, 62, 66).

Levonorgestrel implants. The implant Jadelle (formerly known as Norplant-2) was developed by the Population Council and is manufactured by Schering Oy (formerly Leiras Pharmaceuticals) in Finland. It was first approved in Thailand and Indonesia and later approved in several African countries as well as several Scandinavian and Western European countries and the US. It is available through the private sector in Europe and through national family planning programs in Colombia, Dominican Republic, Ethiopia, Guatemala, Kenya, Mauritius, Panama, Rwanda, Singapore, Yemen, Zambia, and Zimbabwe (106).

Jadelle implants have never been available in the US, however (273). Wyeth, the company that held the distribution license, decided not to market it, and the Population Council is looking for a new US distributor (217).

Jadelle was designed to deliver the same daily dose of levonorgestrel that Norplant delivers, but from two rods instead of six capsules, by releasing the progestin at a higher rate per rod. In a clinical trial of Jadelle involving 1,198 women, none became pregnant in the first four years of use, and 1 per 100 women became pregnant in the fifth year of use (218). Initial effectiveness studies led several countries to label Jadelle as providing three years of protection. Since later studies demonstrated that its contraceptive effect lasts at least five years, many countries, including the US, have now labeled it for five years of use (71, 224). Jadelle’s side effects, continuation rates, and contraceptive effectiveness rates are similar to Norplant’s (2, 61), but Jadelle is easier to insert and remove (218).

The Chinese No. 2 implant system, also called Sinoplant or Sino-implant, and developed by Dahua Pharmaceutical in China, is nearly identical to Jadelle but contains more levonorgestrel (150 instead of 140 mg) (71).

Etonogestrel implants. In 1998, after 12 years of research, Organon launched its etonogestrel implant Implanon (178). Indonesia was the first country to approve Implanon, in 1998. Since then more than 40 European and Asian countries have approved it (273). Organon applied for US FDA approval of Implanon in 2004 and expects approval in 2005 (65).

Implanon consists of a single rod labeled to provide three years of protection from pregnancy, although several studies have found that its contraceptive effect may last at least four years (3, 131). While women using Norplant, Jadelle, or Nestorone have incomplete and inconsistent inhibition of ovulation, Implanon users have few if any ovulatory cycles (148). In clinical trials no women became pregnant over the 5,000 woman-years of study (2, 62).

Nestorone implants. The progestin ST-1435 (also known as Nestorone) is found in the Nestorone implant, which is being developed by the Population Council (214). Effective for two years, the Nestorone implant is a single rod made of a silicone rubber membrane that controls the release rate (68). It is designed specifically for breastfeeding women. Infants of breastfeeding mothers who are using the Nestorone implant have no detectable progestin in their blood (56, 67). The Nestorone implant development program began in the early 1980s (134) and has completed phase II clinical trials. The Population Council is looking for partners to continue the development of this implant (214).

Lactating women have found the Nesterone implant acceptable, but nonlactating women have complained of prolonged and irregular bleeding (219). When the implant was compared with the Copper-T 380A IUD for more than 2,000 woman-months of use by 200 breastfeeding women, no pregnancies occurred in either group, but Nestorone implant users had significantly less irregular bleeding (151).

Bleeding disturbances, including amenorrhea, spotting, and irregular or prolonged bleeding, are the greatest drawbacks of all implants (62, 273). In some clinical trials bleeding disturbances account for up to half of all reasons given for dis- continuation. These side effects usually diminish with con- tinued use, and many women have more regular bleeding patterns after six to nine months of use (57, 61, 87).

The exact mechanism of progestin-induced bleeding disturbances is not completely understood, but implant users experiencing such disturbances are at no more risk of becoming pregnant than users not experiencing them (62). The bleeding patterns reported for different progestin im-plants vary, as do women’s tolerance of bleeding, and it is not possible to predict bleeding patterns for individuals (62).

A review of studies reported that infection or pain at the implant site occurred in less than 7% of users. In an analysis of reported side effects of implants, the most frequent side effects that are probably related to implant use are headaches and acne, both reported by less than 30% of users. Weight gain, dizziness, and mood changes are mentioned by less than 20% of users. Rates of these problems are similar among users of the different implants (40).

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