Birth control pills with three phases versus one phase

Standard birth control pills contain two hormones: progestogen and estrogen. One-phase birth control pills contain the same dose of progestogen and estrogen every day. Four-phase birth control pills contain different amounts of progestogen and estrogen on different days. This review looked at how well one-phase birth control pills and four-phase birth control pills work to prevent pregnancy, how often they cause bleeding problems, how often users experience side effects and how many women stop using the pills.

We did a computer search for randomized controlled trials comparing four-phase birth control pills with one-phase birth control pills. We also wrote to researchers and makers of birth control pills to find other trials. Studies had to report on pregnancy, bleeding problems, side effects or stopping the use of pills. We did not include studies where the pills were used as a treatment for disorders like acne, hirsutism, polycystic ovary syndrome, bleeding problems or endometrioses, or where the pills were administered for less than three months. We assessed whether the studies were conducted properly.

We included one study comparing a four-phase pill composed of the progestogen dienogest and the estrogen estradiol valerate with an one-phase pill composed of the progestogen levonorgestrel and the estrogen ethinylestradiol. Four-phase birth control pills and one-phase birth control pills had similar pregnancy rates. The number of women with blood loss in the period between two menstruations was similar for four-phase pills and one-phase pills. More women using one-phase birth control pills had a menstruation compared to women using four-phase birth control pills. The number of women who stopped using the pills because of side effects was similar for four-phase pills and one-phase pills. Breast pain was reported more frequently by women who used four-phase birth control pills than women who used one-phase birth control pills.

The presence of only one study made it impossible to adequately compare four-phase birth control pills with one-phase birth control pills. More studies are needed to determine whether four-phase pills have advantages over one-phase pills. Until then, we recommend one-phase pills containing 30 μg estrogen for women starting to use birth control pills.

Authors' conclusions: 

The available evidence is insufficient to determine whether quadriphasic differ from monophasic oral contraceptives in contraceptive effectiveness, bleeding pattern, minor side effects and acceptability. Studies that compare quadriphasic and monophasic oral contraceptives with an identical progestogen and estrogen type are needed to determine whether the quadriphasic approach differs from the monophasic approach. Studies that compare quadriphasic pills with monophasic pills containing 30 μg ethinylestradiol are indicated to determine whether quadriphasic oral contraceptives have an advantage over the current, first choice oral contraceptive. Until then, we recommend monophasic pills containing 30 μg estrogen as the first choice for women starting oral contraceptive use.

Read the full abstract...

Quadriphasic oral contraceptives have been developed to reduce the adverse effects of oral contraceptives and are presented as more physiological since they mimic the natural cycle. However, suggested disadvantages of quadriphasic oral contraceptives include a possible increased risk of pill-taking errors caused by the array of different color pills, complicated directions for catching up when a pill is missed, the higher price and potential inferiority in terms of side effects.


To compare the contraceptive effectiveness, bleeding pattern, minor side effects and acceptability of quadriphasic contraceptive pills versus monophasic contraceptive pills.

Search strategy: 

We searched CENTRAL, MEDLINE, EMBASE, POPLINE, and ICTRP for trials comparing quadriphasic pills with monophasic pills. We contacted researchers and manufacturers of quadriphasic oral contraceptives to identify additional studies.

Selection criteria: 

Randomized controlled trials (RCTs) comparing quadriphasic with monophasic oral contraceptives. Trials had to report on contraceptive effectiveness, bleeding patterns, minor side effects, ease of use or trial discontinuation. We excluded studies where the intervention was primarily used as a treatment for disorders or was administered for fewer than three consecutive cycles.

Data collection and analysis: 

Two authors abstracted and entered data into RevMan. We critically appraised the methodological quality of the included trials. For continuous variables, we computed the mean difference with 95% confidence interval (CI) using the random-effects model. For dichotomous variables, we calculated the risk ratio with 95% CI using the random-effects model.

Main results: 

We included one double-blind, double-dummy RCT comparing a quadriphasic oral contraceptive composed of dienogest and estradiol valerate with a monophasic oral contraceptive composed of levonorgestrel and ethinylestradiol. Contraceptive effectiveness, intracyclic bleeding and discontinuation due to side effects were similar for quadriphasic and monophasic pills. The number of women experiencing withdrawal bleeding was higher in the monophasic group compared to the quadriphasic group. Users of quadriphasic pills reported fewer bleeding/spotting days and fewer bleeding/spotting episodes than users of monophasic pills but the report did not specify whether the bleeding/spotting was scheduled or unscheduled. More women using quadriphasic oral contraceptives reported breast pain compared to women using monophasic oral contraceptives.