While COCs containing 20 μg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from existing 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. Higher follow-up rates are essential for meaningful interpretation of results.
Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial.
To compare bleeding patterns between a 21/7-day triphasic norgestimate/ethinyl estradiol (E2) 25-microgram oral contraceptive pill (OCP) and a 24/4-day drospirenone/ethinyl E2 20-microgram OCP.
                In a three-cycle, open-label, multicenter study, healthy, sexually active women were assigned randomly to a 21/7-day (norgestimate/ethinyl E2) or 24/4-day (drospirenone/ethinyl E2) OCP regimen. Randomization was stratified to assure a balanced distribution between regimens for "fresh starts" and "switchers." Bleeding data were collected daily using an interactive voice-response system. Bleeding was defined according to the 2007 U.S. Food and Drug Administration's Reproductive Health Drug Advisory Committee-endorsed criteria.
                Across the three cycles, the 21/7-day OCP group (n=165) reported fewer unscheduled bleeding days than did the 24/4-day OCP group (n=167) (mean 4.6 compared with 6.1 days, P=.003). Women using the 21/7-day OCP had significantly fewer episodes of unscheduled bleeding than did those using the 24/4-day OCP (mean 1.47 compared with 2.01, P=.001). Moreover, women using the 21/7-day OCP had a significantly lower absence of scheduled bleeding at each cycle (P<.001). Both regimens were well-tolerated.
                A 21-day norgestimate/ethinyl E2 25-microgram regimen results in less unscheduled bleeding and more scheduled bleeding than does a 24-day drospirenone/ethinyl E2 20-microgram regimen.
                ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00745901.
                I.