Injectable birth control with both progestin and estrogen

Birth control methods that can be injected may contain two hormones, a progestin and an estrogen. These combined injectable contraceptives (CICs) are effective in preventing pregnancy and can be stopped when a woman wants to get pregnant. This review looked at CICs for how well they prevented pregnancy and for the bleeding patterns and other side effects that may occur. We also studied whether women stopped using them early and whether women liked them.

In January and February 2013, we did computer searches to find randomized trials of combination injectable contraceptives. We included studies that compared a CIC with another birth control method. The other method could be another injectable contraceptive, either combined or having only a progestin. The CIC could also be compared to another hormonal method (like the pill) or to condoms, the diaphragm, or a placebo (or 'dummy').

We found 12 trials that studied four types of CICs. The combined methods required monthly injections. Four trials compared a CIC to 'depo', which has only a progestin. 'Depo' injections should be taken every three months. Five trials compared a CIC with a different combined injectable. Three trials compared a combined injectable with a different dose of the same hormones, with a progestin-only injectable, or with an intrauterine device (IUD).

More women using combined injectables had normal bleeding than women using progestin-only injectables like 'depo.' Also, fewer women using CICs stopped using them because of bleeding reasons than progestin-only users. However, users of combined injectables were more likely to stop using them overall and to stop for other medical reasons. Many factors can affect whether women keep using the method, including whether the women liked it.

Authors' conclusions: 

While 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.

Read the full abstract...

Combination 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.


To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of CICs.

Search strategy: 

In 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 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 criteria: 

RCTs 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 analysis: 

Two 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 results: 

Twelve trials met the inclusion criteria. Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E2C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E2V) 5 mg. 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 E2V 5 mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E2C 5 mg. However, these differences were not detected in all trials. The NET-EN plus E2V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E2C group. The groups did not differ in their amenorrhea rates.