Biphasic versus triphasic oral contraceptives for contraception.
BACKGROUND
Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. A suggested disadvantage of biphasic compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage.


OBJECTIVE
To compare biphasic with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects.


METHODS
We searched computerized databases MEDLINE, EMBASE, POPLINE and the Cochrane Controlled Trials Register (CCTR). In addition, we searched the reference lists of potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA.


METHODS
We included randomized controlled trials comparing any biphasic with any triphasic oral contraceptive when used to prevent pregnancy.


METHODS
We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplemental information about the study methods and outcomes. We entered the data in RevMan 3.1 and later imported it into RevMan 4.1. We calculated Peto odds ratios for incidence of incidence of discontinuation due to medical reasons, intermenstrual bleeding, absence of withdrawal bleeding, and discontinuation due to intermenstrual bleeding.


RESULTS
Only two trials of limited quality met our inclusion criteria. Larranaga (1978) compared two biphasic and one triphasic pills, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. Percival Smith (1990) compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic pill. The odds ratio of cycles with intermenstrual bleeding was 1.7 (95%CI 1.3-2.2) for the biphasic pill compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95%CI 3.1-13). In contrast, cycle control with the biphasic pill was comparable to that with the triphasic pill containing the same progestin (norethindrone).


CONCLUSIONS
The available evidence is limited and of poor quality; the internal validity of these trials is questionable. Given the high losses to follow-up after randomization, these reports may be better considered observational in nature. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. This suggests that the choice of progestin may be more important than the phasic regimen in determining bleeding patterns.
Van Vliet
H A A M
HA
Grimes
D A
DA
Helmerhorst
F M
FM
Schulz
K F
KF
D003267:Contraception; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects; D004997:Ethinyl Estradiol; D005260:Female; D006801:Humans; D016912:Levonorgestrel; D008598:Menstruation / Q000187:drug effects; D009640:Norethindrone; D016032:Randomized Controlled Trials as Topic
D003280:Contraceptives, Oral, Synthetic; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D009640:Norethindrone