20 microg versus >20 microg estrogen combined oral contraceptives for contraception.
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 could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns.


OBJECTIVE
To test the hypothesis that COCs containing </=20 microg ethinyl estradiol (EE) perform similarly as those containing >20 microg in terms of contraceptive effectiveness, bleeding patterns, discontinuation, and side effects.


METHODS
We searched computerized databases (CENTRAL, MEDLINE, EMBASE, and POPLINE) up to January 2008, and searched the references of eligible trials. We wrote to oral contraceptive manufacturers to identify eligible trials.


METHODS
English-language reports of randomized controlled trials were eligible that compare a COC containing </=20 microg EE with a COC containing >20 microg EE. 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.


METHODS
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.


RESULTS
No differences were found in contraceptive effectiveness for the 13 COC pairs for which this outcome was reported. Compared to the higher-estrogen pills, 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 or infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting).


CONCLUSIONS
While COCs containing 20 microg 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.
Division of Reproductive Health, Centers for Disease Control and Prevention, 4770 Buford Highway, Mail Stop K-34, Atlanta, Georgia 30341-3724, USA. mgallo@cdc.gov
Maria F
MF
Gallo
Kavita
K
Nanda
David A
DA
Grimes
Laureen M
LM
Lopez
Kenneth F
KF
Schulz
D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D017135:Desogestrel / Q000008:administration & dosage / Q000009:adverse effects; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008599:Menstruation Disturbances / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic
D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D004967:Estrogens; D004997:Ethinyl Estradiol; D017135:Desogestrel