• Maria F Gallo, David A Grimes, Laureen M Lopez, Kenneth F Schulz, and Catherine d'Arcangues.
• Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
• Cochrane Db Syst Rev. 2013 Jan 1; 3: CD004568.

BackgroundCombination injectable contraceptives (CICs) provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes.ObjectivesTo assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of CICs.Search MethodsIn January and February 2013, we searched for randomized controlled trials (RCTs) of combination injectable contraceptives.Databases include MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS.We searched for current trials in ClinicalTrials.gov and ICTRP.Earlier searches also included AIM and IMEMR. For the initial review, we also assessed the references listed in review articles and in the eligible trial reports.Selection CriteriaRCTs were eligible if they compared a combination injectable contraceptive with any other contraceptive method (e.g., a second CIC,a progestin-only injectable contraceptive, another hormonal contraceptive or a barrier method) or a placebo. We limited the review to marketed CICs.Data Collection And AnalysisTwo authors independently extracted data on contraceptive efficacy, bleeding patterns, continuation, and side effects. We calculated the Peto odds ratio or mean difference with 95% confidence interval for dichotomous or continuous outcome, respectively. Survival analysis estimates for method discontinuation were presented where available.Main ResultsTwelve trials met the inclusion criteria. Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA)25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons.Acceptability results favored the CIC in one study and the progestin-only in another.Studies comparing two CICs found that NET-EN 50 mg plus E(2)V (5)mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials.The NET-EN plus E (2) V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates.Authors' ConclusionsWhile discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward improving the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

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