Biphasic versus monophasic oral contraceptives for contraception.
BACKGROUND
Side effects caused by oral contraceptives discourage compliance with and continuation of oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill.


OBJECTIVE
To compare biphasic with monophasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. Our a priori hypotheses were: (a) biphasic oral contraceptives are less effective than monophasic oral contraceptives in preventing pregnancy, and (b) biphasic oral contraceptives cause more side effects, give poorer cycle control, and have lower continuation rates.


METHODS
We searched the computerized databases MEDLINE, EMBASE, Popline and the Cochrane Controlled Trials Register (CCTR). In addition, we searched the reference lists of all 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 monophasic oral contraceptive when used to prevent pregnancy.


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


RESULTS
Only one trial of limited quality compared a biphasic and monophasic preparation. Percival-Smith et al. (1990) examined 533 user cycles of a biphasic pill (500 mcg norethindrone/35 mcg ethinyl estradiol for 10 days, followed by 1000 mcg norethindrone/35 mcg ethinyl estradiol for 11 days; Ortho 10/11) and 481 user cycles of a monophasic contraceptive pill (1500 norethindrone acetate mcg/30 mcg ethinyl estradiol daily; Loestrin). The study found no significant differences in intermenstrual bleeding, amenorrhea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills.


CONCLUSIONS
Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial, and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.
Van Vliet
H A A M
HA
Family Health International, P. O. Box 13950, Research Triangle Park, North Carolina 27709, USA. dgrimes@fhi.org
Grimes
D A
DA
Helmerhorst
F M
FM
Schulz
K F
KF
D003267:Contraception; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects; D045166:Estradiol Congeners / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000009:adverse effects; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000009:adverse effects; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic
D003280:Contraceptives, Oral, Synthetic; D045166:Estradiol Congeners; D004997:Ethinyl Estradiol; D009640:Norethindrone