Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). This review of randomized controlled trials tested the hypothesis that COCs containing <or=20 microg ethinyl estradiol (EE) perform similarly to those containing >20 microg in terms of contraceptive effectiveness, bleeding patterns, discontinuation and side effects. Data from the 18 eligible trials conducted to date are inadequate for detecting possible differences in contraceptive effectiveness. Several COCs containing 20 microg 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. 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. While health care providers and women might select COCs containing 20 microg EE based on theoretical improvements in safety profile from the reduced dose of estrogen, no evidence is available to support this choice.