20 mcg versus >20 mcg Estrogen combined oral contraceptives for contraception -: art. no. CD003989.pub2

Background Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). However, reducing the amount of estrogen to improve safety also could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns. Objectives To test the hypothesis that COCs containing <= 20 mcg ethinyl estradiol (EE) perform similarly as those containing > 20 mcg in terms of contraceptive effectiveness, bleeding patterns, discontinuation, and side effects. Search strategy We searched computerized databases ( CENTRAL, MEDLINE, EMBASE, and POPLINE) from their inception to November 2003, searched the references of eligible trials, and wrote to oral contraceptive manufacturers to identify eligible trials. Selection criteria English-language reports of randomized controlled trials that compare a COC containing <= 20 mcg EE with a COC containing > 20 mcg EE were eligible. We excluded studies where the interventions were designed to be administered for less than three consecutive cycles or to be used primarily as treatment for non-contraceptive conditions. Trials had to report on contraceptive effectiveness, bleeding patterns, trial discontinuation due to bleeding-related reasons or other side effects, or side effects to be included in the review. Data collection and analysis The primary reviewer evaluated all titles and abstracts located in the literature searches to determine whether they met the inclusion criteria. Two reviewers independently extracted data from the studies identified for inclusion. We wrote to the authors when clarifications or additional data were needed. Data were entered and analyzed with RevMan 4.2. Main results No differences were found in contraceptive effectiveness for the 11 COC pairs for which this outcome was reported. Several COCs containing 20 mcg EE resulted in higher rates of early trial discontinuation ( overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea/infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting) than their higher-estrogen comparison pills. Authors' conclusions While COCs containing 20 mcg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose.