Various Implantable Contraceptives May Be Equally Effective in Preventing Pregnancy  CME

News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD
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July 30, 2007 — Various implantable contraceptives are equally effective in preventing pregnancy, according to the results of a systematic review published online in the July 18 issue of the Cochrane Database of Systematic Reviews.

"Implantable methods of contraception offer long-acting reversible contraception," write Jo Power, MRCOG, MFFP, from the Margaret Pyke Centre in London, United Kingdom, and colleagues. "Their uptake rate in comparison to other contraceptive methods, particularly in developed countries, has historically been low."

The purpose of this review was to compare the contraceptive effectiveness, tolerability, and acceptability of subdermal implants with those of other reversible contraceptive methods. Using database searches, reference lists, and experts in the contraceptive field, the investigators identified randomized controlled trials comparing subdermal implants with other forms of reversible contraceptives. Primary outcomes were pregnancy and continuation rate of contraceptive use in women of childbearing age.

Using a quality checklist to identify general methodologic and contraceptive-specific factors, 2 reviewers independently performed quality assessment of studies and data extraction. Study authors and pharmaceutical companies were contacted to provide additional data concerning pregnancy rates, continuation rate, tolerability, and adverse events.

Of the 9 identified trials, all compared different types of contraceptive implants: 8 (n = 1578) compared Implanon (Organon; Oss, the Netherlands) with Norplant (Wyeth Pharmaceuticals; Madison, New Jersey), and 1 (n = 1198) compared Jadelle (Population Council; New York, NY) with Norplant.

During 4 years of follow-up, contraceptive effectiveness rates and continuation rates for Implanon and Norplant did not differ. Both implants were highly effective contraceptives, with only 2 pregnancies in 4377 women-years of follow-up in Norplant users, 3 in 2307 women-years of follow-up in Jadelle users, and none in 2068 women-years of follow-up in those using Implanon. Pregnancy rates were 0.05, 0.13, and 0 per 100 women-years of use for Norplant, Jadelle, and Implanon, respectively.

Changes in vaginal bleeding pattern were the most frequently reported adverse effect with Implanon and Norplant. The bleeding pattern with Implanon was more variable at first, and, after 2 years of use, the amenorrhea rate was significantly higher with Implanon than with Norplant. With either implant, bleeding decreased with increasing duration of use.

Hormonal adverse effects or adverse events reported in the reviewed trials did not differ significantly with Implanon vs Norplant. Compared with Norplant, Implanon was significantly quicker to insert and to remove.

Jadelle and Norplant did not differ in contraceptive effectiveness or in continuation rates, but Jadelle was significantly quicker to remove than Norplant.

Data concerning failed insertion or failed removal of implants were scarce.

Methodologic problems with the reviewed trials include lack of generalizability to the general population of female contraceptive users, allocation concealment in only 1 of the trials, lack of investigator blinding in most studies, and lack of data on the characteristics of those women who withdrew or were lost to follow-up.

"Although this systematic review was unable to provide a definitive answer on relative effectiveness, tolerability and acceptability of contraceptive implants in comparison to other contraceptive methods, it has raised issues around the conduct of contraceptive research," the authors conclude. "While the comparisons of different types of implants may provide useful information to policy makers and providers of family planning services, they are not necessarily informative to the contraceptive user who wishes to decide between different contraceptive methods."

This review was, in part, funded by the National Health Service Health Technology Assessment Programme. The authors have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online July 18, 2007.

Clinical Context

Subdermal implantable contraceptives have been approved in more than 60 countries and are currently being used by approximately 11 million women worldwide. According to the authors of the current review, this form of contraception is attractive because of its high efficacy, reduced need for active compliance with treatment on the part of the patient, long duration of action, and rapid reversibility on discontinuation of use. However, patients may be less inclined to try subdermal contraceptives because of their relatively high upfront cost and because a special appointment may be necessary with a provider trained in insertion and removal of these devices.

The current review examines the evidence of efficacy and tolerability of subdermal contraceptives.

Study Highlights

• The authors reviewed randomized trials of subdermal contraceptives published in the past 3 decades. They found 9 trials that met inclusion criteria, 8 of which compared Implanon vs Norplant and 1 of which compared Jadelle vs Norplant.
• Although it was not possible to determine single-decrement life-table probabilities of contraceptive efficacy and tolerability, the number of pregnancies per months of use per woman was calculated across different trials. Menstrual changes associated with treatment were assessed if they were measured in 90-day intervals.
• 1578 women were included in the trials of Implanon vs Norplant, and 1198 women comprised the study cohort in the trial of Norplant vs Jadelle. Women in these studies were aged between 18 and 40 years.
• There were some methodologic flaws common to many of the trials, particularly a lack of detail regarding the method of randomization and allocation concealment.
• There was no difference between Implanon and Norplant in terms of efficacy. There were no pregnancies reported after 26,972 and 28,108 women-months of follow-up, respectively.
• There was no significant difference between Implanon and Norplant in treatment continuation at 1, 2, 3, or 4 years. Respective rates of treatment continuation were 67.4% and 72.5% at year 3 and 17.1% and 16.9% at year 4. Women in developing countries were more likely to continue using the subdermal contraceptive vs those in developed countries.
• Menstrual changes were common with both Implanon and Norplant, but rates of this most common adverse event were similar between these therapies. Infrequent and prolonged bleeding were slightly more common with Implanon vs Norplant shortly after initiation of contraception, but Implanon was also associated with slightly higher rates of amenorrhea with prolonged use.
• It was not possible to extract data regarding discontinuation of treatment caused by abnormal bleeding. Other common adverse effects associated with subdermal contraception included acne, headaches, breast pain, and increase in body weight. There was no significant difference between Implanon and Norplant in the rate of these adverse events or rates of discontinuation of treatment caused by adverse events.
• The mean times for the insertion of Implanon and Norplant were 1.1 and 4.3 minutes, respectively. The respective mean times for removal of the devices were 2.6 and 10.2 minutes. Women who received Norplant were more likely to have difficulty with removal of their device vs those who received Implanon (4.8% vs 0.2%, respectively).
• In the 1 study comparing Jadelle vs Norplant, both treatments were similarly effective in preventing pregnancy and had similar discontinuation rates caused by adverse events. Jadelle required less time to remove vs Norplant.

Pearls for Practice

• Compared with other contraceptives, subdermal contraceptives offer high efficacy, low need for compliance, rapid reversibility, and a long duration of action. However, the initial cost of these contraceptive methods may be high.
• The current review shows that Implanon and Norplant are both very effective in preventing pregnancy and have similar tolerability profiles. Implanon generally has faster insertion and removal times vs Norplant.

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