A Cochrane review included 21 studies. English-language reports of randomized controlled trials that compare a COC containing 20 mcg EE with a COC containing >20 mcg EE were eligible. No differences were found in contraceptive effectiveness for the 13 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.
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, lack of blinding, and more than 20% loss to follow up).