Birth control pills with two phases versus three phases

Side effects of birth control pills may keep women from using them as planned. Attempts to decrease side effects led to the three-phase pill in the 1980s. Pills with phases provide different amounts of hormones over three weeks. Whether three-phase pills lead to fewer pregnancies than two-phase pills is unknown. Nor is it known if the pills give better cycle control or have fewer side effects. This review looked at whether two-phase pills worked as well as three-phase pills. We also studied whether women had fewer side effects with these pills.

We did a computer search for studies of birth control pills with two phases versus pills with three phases. We also wrote to researchers and manufacturers to find other trials. We included randomized trials in any language.

We found only two trials that looked at two-phase versus three-phase birth control pills. The studies did not have good methods and the authors did not report all their methods. Many women dropped out of the studies, which affects what can be said about the results. One study compared two types of two-phase pills with a three-phase pill. The pills did not differ in any major ways, including the numbers of women who stopped using the pills due to health problems. The other trial compared a two-phase pill with two different three-phase pills. The two-phase pill had worse bleeding patterns than the three-phase pill with a different hormone (levonorgestrel). In contrast, bleeding with the two-phase pill was like that of the three-phase pill with the same hormone (norethindrone). The type of hormone may be more important than the phases for cycle control.

These trials did not provide enough evidence to say if three-phase pills worked any better than two-phase types for birth control, bleeding patterns, or staying on the pill. More research would be needed to show whether three-phase pills were better than two-phase pills. However, two-phase pills are not used enough to justify further research.

Authors' conclusions: 

The available evidence is limited and the internal validity of these trials is questionable. Given the high losses to follow up, these reports may even be considered observational. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. The choice of progestin may be more important than the phasic regimen in determining bleeding patterns.

Read the full abstract...
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 (OC) pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage.

Objectives: 

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

Search strategy: 

We searched MEDLINE, POPLINE, LILACS and CENTRAL, as well as clinical trials databases (ClinicalTrials.gov and ICTRP). We searched the reference lists of relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies.

Selection criteria: 

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

Data collection and analysis: 

We examined the studies found during the searches for inclusion and assessed methodological quality. We contacted the authors of included studies and of possibly randomized studies for information about the methods and outcomes. We entered the data into RevMan. We calculated Peto odds ratios for incidence of discontinuation due to medical reasons, intermenstrual bleeding, and absence of withdrawal bleeding.

Main results: 

Only two trials of limited quality met our inclusion criteria. One study compared two biphasic pills and one triphasic pill, 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. The other trial compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and with another triphasic containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic. The odds ratio of cycles with intermenstrual bleeding was 1.70 (95% confidence interval (CI) 1.29 to 2.24) for the biphasic compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.48 (95% CI 3.13 to 13.39). In contrast, cycle control with the biphasic pill was comparable to that of the triphasic containing the same progestin (norethindrone).